Potencial efecto neuroprotector de los agonistas LXR en la activación de autofagia de células gliales y neuronales sometidas a privación de glucosa y oxígeno

dc.contributor.advisorArboleda Bustos, Gonzalo Humberto
dc.contributor.authorVargas Moreno, Monica Alexandra
dc.contributor.researchgroupGrupo de Neurociencias-Universidad Nacional de Colombiaspa
dc.date.accessioned2023-07-27T21:32:25Z
dc.date.available2023-07-27T21:32:25Z
dc.date.issued2023-07-26
dc.descriptionilustraciones, diagramas, fotografíasspa
dc.description.abstractLa enfermedad cerebrovascular es una de las causas más relevantes de morbimortalidad en el mundo. Por ello es de gran importancia el entendimiento de los mecanismos fisiopatológicos de esta enfermedad, que permitan encontrar blancos terapéuticos para mejorar la sobrevida neuronal que prosigue a la lesión isquémica. Clásicamente se hablaba de 2 tipos de muerte celular relacionadas con este tipo de lesión: necrosis y apoptosis; sin embargo, recientemente se ha encontrado una gran variedad morfológica de tipos adicionales de muerte celular, entre estas, la asociada a autofagia ha tomado gran importancia en la última década. Existe evidencia reciente del efecto neuroprotector de los agonistas de receptores X del hígado (LXR: por sus siglas en inglés, Liver X receptors) en escenarios de isquemia cerebral y de su capacidad de modular la activación de la autofagia. Se ha descrito también el papel que cumplen las células gliales en el daño neuronal que prosigue a la lesión isquémica. Debido a esto, se planteó como objetivo general analizar el efecto de agonistas LXR en la activación de procesos de autofagia en células gliales y neuronales expuestas a privación de glucosa y oxígeno como un posible blanco terapéutico para modular la respuesta celular deletérea post isquemia. Se desarrolló un modelo in vitro de isquemia celular con líneas celulares y cultivo primario de neuronas y células gliales de corteza de ratón expuestas a privación de glucosa y oxígeno pretratadas con un extracto de plantas colombianas con actividad agonista LXR, Zanthoxylum caribaeum. Encontrando que el pretratamiento con las fracciones en estudio ofrece protección ante la privación combinada de glucosa y oxígeno en líneas celulares y células gliales de cultivo primario y en estas últimas podría activar vías de autofagia evidenciado en el aumentó de los niveles de LC3II. (Texto tomado de la fuente)spa
dc.description.abstractCerebrovascular disease is one of the most relevant causes of morbimortality in the world. Therefore, the understanding of the physio pathological disease mechanisms that will allow the acquisition of therapeutic targets to improve neuronal survival after an ischemic lesion is of the utmost importance. Traditionally, two types of cell death were associated with this kind of lesion: necrosis and apoptosis, however as of late a great variety of morphological types of cellular death has been found, among those, the one associated with autophagy has gained great importance in the last decade. There is recent evidence of the neuroprotective effect of the Liver X receptor (LXR) agonists in scenarios of cerebral ischemia and their ability to modulate autophagy activation. The role of glial cells in neuronal damage after an ischemic injury has also been described. Due to this, the analyzing the effect of the LXR agonists on the activation of the autophagy processes on glial and neuronal cells exposed to glucose and oxygen deprivation as a possible therapeutic target to modulate the deleterious post ischemic cell response was proposed as a primary objective. An in vitro model of cellular ischemia was developed, using cell lines, neuron primary cultures, as well as glial cortex cells obtained from mice, all of which were exposed to glucose and oxygen deprivation and pretreated with and extract obtained from Colombian plants with an LXR agonist activity, Zanthoxylum caribaeum. We found that pretreatment with the studied fractions confers protection against the combined deprivation of glucose and oxygen in cell lines and in primary culture glial cells, and in the latter, might activate autophagy pathways, as demonstrated by an increase in LC3II levels.eng
dc.description.degreelevelMaestríaspa
dc.description.degreenameMagíster en Neurocienciasspa
dc.description.researchareaMuerte celularspa
dc.format.extent94 páginasspa
dc.format.mimetypeapplication/pdfspa
dc.identifier.instnameUniversidad Nacional de Colombiaspa
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombiaspa
dc.identifier.repourlhttps://repositorio.unal.edu.co/spa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/84339
dc.language.isospaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.facultyFacultad de Medicinaspa
dc.publisher.placeBogotá,Colombiaspa
dc.publisher.programBogotá - Medicina - Maestría en Neurocienciasspa
dc.relation.referencesAgrotis, A., Pengo, N., Burden, J. J., & Ketteler, R. (2019). Redundancy of human ATG4 protease isoforms in autophagy and LC3/GABARAP processing revealed in cells. Autophagy, 15(6), 976–997. https://doi.org/10.1080/15548627.2019.1569925spa
dc.relation.referencesAhsan, A., Liu, M., Zheng, Y., Yan, W., Pan, L., Li, Y., Ma, S., Zhang, X., Cao, M., Wu, Z., Hu, W., Chen, Z., & Zhang, X. (2021). Natural compounds modulate the autophagy with potential implication of stroke. Acta pharmaceutica Sinica. B, 11(7), 1708–1720. https://doi.org/10.1016/j.apsb.2020.10.018spa
dc.relation.referencesAmado, B., Melo, L., Pinto, R., Lobo, A., Barros, P., & Gomes, J. R. (2022). Ischemic Stroke, Lessons from the Past towards Effective Preclinical Models. Biomedicines, 10(10), 2561. https://doi.org/10.3390/biomedicines10102561spa
dc.relation.referencesAvezum, Á., Costa-Filho, F. F., Pieri, A., Martins, S. O., & Marin-Neto, J. A. (2015). Stroke in Latin America: Burden of Disease and Opportunities for Prevention. Global heart, 10(4), 323–331. https://doi.org/10.1016/j.gheart.2014.01.006spa
dc.relation.referencesBalduini, W., Carloni, S., & Buonocore, G. (2012). Autophagy in hypoxia-ischemia induced brain injury. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 25 Suppl 1, 30–34. https://doi.org/10.3109/14767058.2012.663176spa
dc.relation.referencesBeaudoin, G. M., 3rd, Lee, S. H., Singh, D., Yuan, Y., Ng, Y. G., Reichardt, L. F., & Arikkath, J. (2012). Culturing pyramidal neurons from the early postnatal mouse hippocampus and cortex. Nature protocols, 7(9), 1741–1754. https://doi.org/10.1038/nprot.2012.099spa
dc.relation.referencesBento, C. F., Renna, M., Ghislat, G., Puri, C., Ashkenazi, A., Vicinanza, M., … Rubinsztein, D. C. (2016). Mammalian Autophagy: How Does It Work? Annual Review of Biochemistry, 85(1), 685–713. doi:10.1146/annurev-biochem-060815-014556spa
dc.relation.referencesBroughton, B. R., Reutens, D. C., & Sobey, C. G. (2009). Apoptotic mechanisms after cerebral ischemia. Stroke, 40(5), e331–e339. https://doi.org/10.1161/STROKEAHA.108.531632spa
dc.relation.referencesBuckley, K. M., Hess, D. L., Sazonova, I. Y., Periyasamy-Thandavan, S., Barrett, J. R., Kirks, R., Grace, H., Kondrikova, G., Johnson, M. H., Hess, D. C., Schoenlein, P. V., Hoda, M. N., & Hill, W. D. (2014). Rapamycin up-regulation of autophagy reduces infarct size and improves outcomes in both permanent MCAL, and embolic MCAO, murine models of stroke. Experimental & translational stroke medicine, 6, 8. https://doi.org/10.1186/2040-7378-6-8spa
dc.relation.referencesCasals, J. B., Pieri, N. C., Feitosa, M. L., Ercolin, A. C., Roballo, K. C., Barreto, R. S., Bressan, F. F., Martins, D. S., Miglino, M. A., & Ambrósio, C. E. (2011). The use of animal models for stroke research: a review. Comparative medicine, 61(4), 305–313.spa
dc.relation.referencesCarloni, S., Buonocore, G., & Balduini, W. (2008). Protective role of autophagy in neonatal hypoxia-ischemia induced brain injury. Neurobiology of disease, 32(3), 329–339. https://doi.org/10.1016/j.nbd.2008.07.022spa
dc.relation.referencesChapuisat, G., Dronne, M. A., Grenier, E., Hommel, M., & Boissel, J. P. (2010). In silico study of the influence of intensity and duration of blood flow reduction on cell death through necrosis or apoptosis during acute ischemic stroke. Acta biotheoretica, 58(2-3), 171–190. https://doi.org/10.1007/s10441-010-9100-2spa
dc.relation.referencesChen, J., Zacharek, A., Cui, X., Shehadah, A., Jiang, H., Roberts, C., Lu, M., & Chopp, M. (2010). Treatment of stroke with a synthetic liver X receptor agonist, TO901317, promotes synaptic plasticity and axonal regeneration in mice. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 30(1), 102–109. https://doi.org/10.1038/jcbfm.2009.187spa
dc.relation.referencesChen, W., Sun, Y., Liu, K., & Sun, X. (2014). Autophagy: a double-edged sword for neuronal survival after cerebral ischemia. Neural Regeneration Research, 9(12), 1210–1216. http://doi.org/10.4103/1673-5374.135329spa
dc.relation.referencesCheng, O., Ostrowski, R. P., Liu, W., & Zhang, J. H. (2010). Activation of liver X receptor reduces global ischemic brain injury by reduction of nuclear factor-kappaB. Neuroscience, 166(4), 1101–1109. https://doi.org/10.1016/j.neuroscience.2010.01.024spa
dc.relation.referencesChu C. T. (2006). Autophagic stress in neuronal injury and disease. Journal of neuropathology and experimental neurology, 65(5), 423–432. https://doi.org/10.1097/01.jnen.0000229233.75253.bespa
dc.relation.referencesCui, X., Chopp, M., Zacharek, A., Cui, Y., Roberts, C., & Chen, J. (2013). The neurorestorative benefit of GW3965 treatment of stroke in mice. Stroke, 44(1), 153–161. https://doi.org/10.1161/STROKEAHA.112.677682spa
dc.relation.referencesDeng, Y. H., He, H. Y., Yang, L. Q., & Zhang, P. Y. (2016). Dynamic changes in neuronal autophagy and apoptosis in the ischemic penumbra following permanent ischemic stroke. Neural regeneration research, 11(7), 1108–1114. doi:10.4103/1673-5374.187045spa
dc.relation.referencesDikic I, Elazar Z (2018). Mechanism and medical implications of mammalian autophagy.Nat Rev Mol Cell Biol 19, 349–364. https://doi.org/10.1038/s41580-018-0003-4spa
dc.relation.referencesDing, C., Zhang, J., Li, B., Ding, Z., Cheng, W., Gao, F., Zhang, Y., Xu, Y., & Zhang, S. (2018). Cornin protects SH‑SY5Y cells against oxygen and glucose deprivation‑induced autophagy through the PI3K/Akt/mTOR pathway. Molecular medicine reports, 17(1), 87–92. https://doi.org/10.3892/mmr.2017.7864spa
dc.relation.referencesDu, Y., Deng, W., Wang, Z., Ning, M., Zhang, W., Zhou, Y., Lo, E. H., & Xing, C. (2017). Differential subnetwork of chemokines/cytokines in human, mouse, and rat brain cells after oxygen-glucose deprivation. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 37(4), 1425–1434. https://doi.org/10.1177/0271678X16656199spa
dc.relation.referencesDuque, A. A., & Lucumi, D. I. (2019). Caracterización del accidente cerebrovascular en colombia (N.o 63). Escuela de Gobierno Alberto Lleras Camargo, Universidad de los Andes. https://repositorio.uniandes.edu.co/bitstream/handle/1992/40736/Caracterizaci%C3%B3n-accidente.pdf?sequence=1spa
dc.relation.referencesFaysel, M. A., Singer, J., Cummings, C., Stefanov, D. G., & Levine, S. R. (2019). Disparities in the Use of Intravenous t-PA among Ischemic Stroke Patients: Population-based Recent Temporal Trends. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, 28(5), 1243–1251. https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.01.013spa
dc.relation.referencesFriedman, L. G., Lachenmayer, M. L., Wang, J., He, L., Poulose, S. M., Komatsu, M., Holstein, G. R., & Yue, Z. (2012). Disrupted autophagy leads to dopaminergic axon and dendrite degeneration and promotes presynaptic accumulation of α-synuclein and LRRK2 in the brain. The Journal of neuroscience : the official journal of the Society for Neuroscience, 32(22), 7585–7593. https://doi.org/10.1523/JNEUROSCI.5809-11.2012spa
dc.relation.referencesGandolfi, M., Smania, N., Vella, A., Picelli, A., & Chirumbolo, S. (2017). Assessed and Emerging Biomarkers in Stroke and Training-Mediated Stroke Recovery: State of the Art. Neural Plasticity, 2017, 1389475. http://doi.org/10.1155/2017/1389475spa
dc.relation.referencesGao, L., Jiang, T., Guo, J., Liu, Y., Cui, G., Gu, L., Zhang, Y. (2012). Inhibition of Autophagy Contributes to Ischemic Postconditioning-Induced Neuroprotection against Focal Cerebral Ischemia in Rats. PLoS ONE, 7(9), e46092. http://doi.org/10.1371/journal.pone.0046092spa
dc.relation.referencesGiordano, G., & Costa, L. G. (2011). Primary neurons in culture and neuronal cell lines for in vitro neurotoxicological studies. Methods in molecular biology (Clifton, N.J.), 758, 13–27. https://doi.org/10.1007/978-1-61779-170-3_2spa
dc.relation.referencesGlick, D., Barth, S., & Macleod, K. F. (2010). Autophagy: cellular and molecular mechanisms. The Journal of pathology, 221(1), 3–12. doi:10.1002/path.2697spa
dc.relation.referencesGómez-Sánchez, R., Pizarro-Estrella, E., Yakhine-Diop, S. M., Rodríguez-Arribas, M., Bravo-San Pedro, J. M., Fuentes, J. M., & González-Polo, R. A. (2015). Routine Western blot to check autophagic flux: cautions and recommendations. Analytical biochemistry, 477, 13–20. https://doi.org/10.1016/j.ab.2015.02.020spa
dc.relation.referencesGuzik, A., & Bushnell, C. (2017). Stroke Epidemiology and Risk Factor Management. Continuum (Minneapolis, Minn.), 23(1, Cerebrovascular Disease), 15–39.spa
dc.relation.referencesHa, J., Guan, K. L., & Kim, J. (2015). AMPK and autophagy in glucose/glycogen metabolism. Molecular aspects of medicine, 46, 46–62. https://doi.org/10.1016/j.mam.2015.08.002spa
dc.relation.referencesHaque, M. N., Hannan, M. A., Dash, R., Choi, S. M., & Moon, I. S. (2021). The potential LXRβ agonist stigmasterol protects against hypoxia/reoxygenation injury by modulating mitophagy in primary hippocampal neurons. Phytomedicine : international journal of phytotherapy and phytopharmacology, 81, 153415. https://doi.org/10.1016/j.phymed.2020.153415spa
dc.relation.referencesHaque, M. N., Hannan, M. A., Dash, R., Choi, S. M., & Moon, I. S. (2021). The potential LXRβ agonist stigmasterol protects against hypoxia/reoxygenation injury by modulating mitophagy in primary hippocampal neurons. Phytomedicine : international journal of phytotherapy and phytopharmacology, 81, 153415. https://doi.org/10.1016/j.phymed.2020.153415spa
dc.relation.referencesHarnett, M. M., Pineda, M. A., Latré de Laté, P., Eason, R. J., Besteiro, S., Harnett, W., & Langsley, G. (2017). From Christian de Duve to Yoshinori Ohsumi: More to autophagy than just dining at home. Biomedical journal, 40(1), 9–22. doi:10.1016/j.bj.2016.12.004.spa
dc.relation.referencesHolloway, P. M., & Gavins, F. N. (2016). Modeling Ischemic Stroke In Vitro: Status Quo and Future Perspectives. Stroke, 47(2), 561–569. https://doi.org/10.1161/STROKEAHA.115.011932spa
dc.relation.referencesHu, S., Wu, G., Ding, X., & Zhang, Y. (2016). Thrombin preferentially induces autophagy in glia cells in the rat central nervous system. Neuroscience letters, 630, 53–58. https://doi.org/10.1016/j.neulet.2016.07.023spa
dc.relation.referencesItakura, E., Kishi-Itakura, C., & Mizushima, N. (2012). The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes. Cell, 151(6), 1256–1269. https://doi.org/10.1016/j.cell.2012.11.001spa
dc.relation.referencesJia, Z., Dong, A., Che, H., & Zhang, Y. (2017). 17-DMAG Protects Against Hypoxia-/Reoxygenation-Induced Cell Injury in HT22 Cells Through Akt/Nrf2/HO-1 Pathway. DNA and cell biology, 36(2), 95–102. https://doi.org/10.1089/dna.2016.3445spa
dc.relation.referencesJuntunen, M., Hagman, S., Moisan, A., Narkilahti, S., & Miettinen, S. (2020). In Vitro Oxygen-Glucose Deprivation-Induced Stroke Models with Human Neuroblastoma Cell- and Induced Pluripotent Stem Cell-Derived Neurons. Stem cells international, 2020, 8841026. https://doi.org/10.1155/2020/8841026spa
dc.relation.referencesKabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, et al. (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19: 5720–5728spa
dc.relation.referencesKasprowska, D., Machnik, G., Kost, A., & Gabryel, B. (2017). Time-Dependent Changes in Apoptosis Upon Autophagy Inhibition in Astrocytes Exposed to Oxygen and Glucose Deprivation. Cellular and molecular neurobiology, 37(2), 223–234. https://doi.org/10.1007/s10571-016-0363-2spa
dc.relation.referencesKaushik, S., Cuervo, A. M. (2018). The coming of age of chaperone-mediated autophagy. Nature reviews. Molecular cell biology, 19(6), 365–381. https://doi.org/10.1038/s41580-018-0001-6spa
dc.relation.referencesKikuchi, K., Uchikado, H., Morioka, M., Murai, Y., & Tanaka, E. (2012). Clinical neuroprotective drugs for treatment and prevention of stroke. International journal of molecular sciences, 13(6), 7739–7761. doi:10.3390/ijms13067739spa
dc.relation.referencesKlionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., Adamopoulos, I. E., Adeli, K., Adolph, T. E., Adornetto, A., Aflaki, E., Agam, G., Agarwal, A., Aggarwal, B. B., Agnello, M., Agostinis, P., … Tong, C. K. (2021). Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1. Autophagy, 17(1), 1–382. https://doi.org/10.1080/15548627.2020.1797280spa
dc.relation.referencesKomatsu, M., Waguri, S., Ueno, T., Iwata, J., Murata, S., Tanida, I., Ezaki, J., Mizushima, N., Ohsumi, Y., Uchiyama, Y., Kominami, E., Tanaka, K., & Chiba, T. (2005). Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. The Journal of cell biology, 169(3), 425–434. https://doi.org/10.1083/jcb.200412022spa
dc.relation.referencesKoukourakis, M. I., Kalamida, D., Giatromanolaki, A., Zois, C. E., Sivridis, E., Pouliliou, S., Mitrakas, A., Gatter, K. C., & Harris, A. L. (2015). Autophagosome Proteins LC3A, LC3B and LC3C Have Distinct Subcellular Distribution Kinetics and Expression in Cancer Cell Lines. PloS one, 10(9), e0137675. https://doi.org/10.1371/journal.pone.0137675spa
dc.relation.referencesKuma, A., Komatsu, M., & Mizushima, N. (2017). Autophagy-monitoring and autophagy-deficient mice. Autophagy, 13(10), 1619–1628. doi:10.1080/15548627.2017.1343770spa
dc.relation.referencesLakhan, S. E., Kirchgessner, A., & Hofer, M. (2009). Inflammatory mechanisms in ischemic stroke: therapeutic approaches. Journal of translational medicine, 7, 97. https://doi.org/10.1186/1479-5876-7-97spa
dc.relation.referencesLewis, G. F., & Rader, D. J. (2005). New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circulation research, 96(12), 1221–1232. https://doi.org/10.1161/01.RES.0000170946.56981.5cspa
dc.relation.referencesLi, H., Qiu, S., Li, X., Li, M., & Peng, Y. (2015). Autophagy biomarkers in CSF correlates with infarct size, clinical severity and neurological outcome in AIS patients. Journal of Translational Medicine, 13, 359. http://doi.org/10.1186/s12967-015-0726-3spa
dc.relation.referencesLiang XH, Jackson S, Seaman M, Brown K, Kempkes B, et al. (1999) Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402: 672–676spa
dc.relation.referencesLi, H., Qiu, S., Li, X., Li, M., & Peng, Y. (2015). Autophagy biomarkers in CSF correlates with infarct size, clinical severity and neurological outcome in AIS patients. Journal of translational medicine, 13, 359. https://doi.org/10.1186/s12967-015-0726-3spa
dc.relation.referencesLiu, P., He, S., Gao, J., Li, J., Fan, X., & Xiao, Y.-B. (2014). Liver X receptor activation protects against inflammation and enhances autophagy in myocardium of neonatal mouse challenged by lipopolysaccharides. Bioscience, Biotechnology, and Biochemistry, 78(9), 1504–1513.spa
dc.relation.referencesLiu, X., Tian, F., Wang, S., Wang, F., & Xiong, L. (2018). Astrocyte Autophagy Flux Protects Neurons Against Oxygen-Glucose Deprivation and Ischemic/Reperfusion Injury. Rejuvenation research, 21(5), 405–415. https://doi.org/10.1089/rej.2017.1999spa
dc.relation.referencesLong, H. Z., Cheng, Y., Zhou, Z. W., Luo, H. Y., Wen, D. D., & Gao, L. C. (2021). PI3K/AKT Signal Pathway: A Target of Natural Products in the Prevention and Treatment of Alzheimer's Disease and Parkinson's Disease. Frontiers in pharmacology, 12, 648636. https://doi.org/10.3389/fphar.2021.648636spa
dc.relation.referencesLyden P. D. (2021). Cerebroprotection for Acute Ischemic Stroke: Looking Ahead. Stroke, 52(9), 3033–3044. https://doi.org/10.1161/STROKEAHA.121.032241spa
dc.relation.referencesMarchus, C. R. N., Knudson, J. A., Morrison, A. E., Strawn, I. K., Hartman, A. J., Shrestha, D., Pancheri, N. M., Glasgow, I., & Schiele, N. R. (2021). Low-cost, open-source cell culture chamber for regulating physiologic oxygen levels. HardwareX, 11, e00253. https://doi.org/10.1016/j.ohx.2021.e00253spa
dc.relation.referencesMaruyama, T., & Noda, N. N. (2017). Autophagy-regulating protease Atg4: structure, function, regulation and inhibition. The Journal of antibiotics, 71(1), 72–78. Advance online publication. https://doi.org/10.1038/ja.2017.104spa
dc.relation.referencesMizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y. 2004. In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol. Biol. Cell 15:1101–11spa
dc.relation.referencesMulder, I. A., van Bavel, E. T., de Vries, H. E., & Coutinho, J. M. (2021). Adjunctive cytoprotective therapies in acute ischemic stroke: a systematic review. Fluids and barriers of the CNS, 18(1), 46. https://doi.org/10.1186/s12987-021-00280-1spa
dc.relation.referencesNguyen, T. N., Padman, B. S., Usher, J., Oorschot, V., Ramm, G., & Lazarou, M. (2016). Atg8 family LC3/GABARAP proteins are crucial for autophagosome–lysosome fusion but not autophagosome formation during PINK1/Parkin mitophagy and starvation. The Journal of Cell Biology, 215(6), 857–874. http://doi.org/10.1083/jcb.201607039spa
dc.relation.referencesOliva Trejo, J. A., Tanida, I., Suzuki, C., Kakuta, S., Tada, N., & Uchiyama, Y. (2020). Characterization of starvation-induced autophagy in cerebellar Purkinje cells of pHluorin-mKate2-human LC3B transgenic mice. Scientific reports, 10(1), 9643. https://doi.org/10.1038/s41598-020-66370-6spa
dc.relation.referencesPipicano Ordoñez, P. A. (2016). Evaluación del precondicionamiento hipóxico como un mecanismo protector en cultivos primarios neuronales de rata wistar. Universidad ICESI. Prasad, A., Kumar, S. S., Dessimoz, C., Bleuler, S., Laule, O., Hruz, T., Gruissem, W., & Zimmermann, P. (2013). Global regulatory architecture of human, mouse and rat tissue transcriptomes. BMC genomics, 14, 716. https://doi.org/10.1186/1471-2164-14-716spa
dc.relation.referencesQin, A. P., Liu, C. F., Qin, Y. Y., Hong, L. Z., Xu, M., Yang, L., Liu, J., Qin, Z. H., & Zhang, H. L. (2010). Autophagy was activated in injured astrocytes and mildly decreased cell survival following glucose and oxygen deprivation and focal cerebral ischemia. Autophagy, 6(6), 738–753. https://doi.org/10.4161/auto.6.6.12573spa
dc.relation.referencesQin, C., Yang, S., Chu, Y. H., Zhang, H., Pang, X. W., Chen, L., Zhou, L. Q., Chen, M., Tian, D. S., & Wang, W. (2022). Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions. Signal transduction and targeted therapy, 7(1), 215. https://doi.org/10.1038/s41392-022-01064-1spa
dc.relation.referencesRami A. (2008). Upregulation of Beclin 1 in the ischemic penumbra. Autophagy, 4(2), 227–229. https://doi.org/10.4161/auto.5339 Ravanan, P., Srikumar, I. F., & Talwar, P. (2017). Autophagy: The spotlight for cellular stress responses. Life Sciences, 188, 53–67. doi:10.1016/j.lfs.2017.08.029spa
dc.relation.referencesRoth, G. A., Mensah, G. A., Johnson, C. O., Addolorato, G., Ammirati, E., Baddour, L. M., Barengo, N. C., Beaton, A. Z., Benjamin, E. J., Benziger, C. P., Bonny, A., Brauer, M., Brodmann, M., Cahill, T. J., Carapetis, J., Catapano, A. L., Chugh, S. S., Cooper, L. T., Coresh, J., Criqui, M., … GBD-NHLBI-JACC Global Burden of Cardiovascular Diseases Writing Group (2020). Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study. Journal of the American College of Cardiology, 76(25), 2982–3021. https://doi.org/10.1016/j.jacc.2020.11.010spa
dc.relation.referencesRyou M, Mallet R (2018) An in vitro Oxygen-Glucose deprivation model for studying ischemia - Reperfusion Injury of neuronal cells chapter 18 at Binu Tharakan (ed.), Traumatic and Ischemic Injury: Methods and Protocols, Methods in Molecular Biology vol. 1717,https://doi.org/10.1007/978-1-4939-7526-6_18, © Springer Science+Business Media, LLCspa
dc.relation.referencesSaha, S., Panigrahi, D. P., Patil, S., & Bhutia, S. K. (2018). Autophagy in health and disease: A comprehensive review. Biomedicine & Pharmacotherapy, 104, 485–495.doi:10.1016/j.biopha.2018.05.007spa
dc.relation.referencesSaxena, S, Agrawal, I, Singh, P, Jha, S. Portable, low-cost hypoxia chamber for simulating hypoxic environments: Development, characterization and applications. Med Devices Sens. 2020; 3:e10064. https://doi.org/10.1002/mds3.10064spa
dc.relation.referencesSegala, G., David, M., de Medina, P., Poirot, M. C., Serhan, N., Vergez, F., … Silvente-Poirot, S. (2017). Dendrogenin A drives LXR to trigger lethal autophagy in cancers. Nature communications, 8(1), 1903. doi:10.1038/s41467-017-01948-9spa
dc.relation.referencesSekerdag, E., Solaroglu, I., & Gursoy-Ozdemir, Y. (2018). Cell Death Mechanisms in Stroke and Novel Molecular and Cellular Treatment Options. Current neuropharmacology, 16(9), 1396–1415. https://doi.org/10.2174/1570159X16666180302115544spa
dc.relation.referencesSironi, L., Mitro, N., Cimino, M., Gelosa, P., Guerrini, U., Tremoli, E., & Saez, E. (2008). Treatment with LXR agonists after focal cerebral ischemia prevents brain damage. FEBS letters, 582(23-24), 3396–3400. https://doi.org/10.1016/j.febslet.2008.08.035spa
dc.relation.referencesSmith, B. A., & Smith, B. D. (2012). Biomarkers and molecular probes for cell death imaging and targeted therapeutics. Bioconjugate chemistry, 23(10), 1989–2006. doi:10.1021/bc3003309spa
dc.relation.referencesSmith, C. M., Chen, Y., Sullivan, M. L., Kochanek, P. M., & Clark, R. S. B. (2011). Autophagy in Acute Brain Injury: Feast, Famine, or Folly? Neurobiology of Disease, 43(1), 52–59. http://doi.org/10.1016/j.nbd.2010.09.014.spa
dc.relation.referencesSommer C. J. (2017). Ischemic stroke: experimental models and reality. Acta neuropathologica, 133(2), 245–261. https://doi.org/10.1007/s00401-017-1667-0spa
dc.relation.referencesSun, T., Li, Y. J., Tian, Q. Q., Wu, Q., Feng, D., Xue, Z., Guo, Y. Y., Yang, L., Zhang, K., Zhao, M. G., & Wu, Y. M. (2018). Activation of liver X receptor β-enhancing neurogenesis ameliorates cognitive impairment induced by chronic cerebral hypoperfusion. Experimental neurology, 304, 21–29. https://doi.org/10.1016/j.expneurol.2018.02.006spa
dc.relation.referencesSuzuki. H, Osawa. T, Fujioka. Y, Noda. N. (2017) Structural biology of the core autophagy machineryCurr. Opin. Struct. Biol., 43, pp. 10-17spa
dc.relation.referencesTasca, C. I., Dal-Cim, T., & Cimarosti, H. (2015). In vitro oxygen-glucose deprivation to study ischemic cell death. Methods in molecular biology (Clifton, N.J.), 1254, 197–210. https://doi.org/10.1007/978-1-4939-2152-2_15spa
dc.relation.referencesTian, F., Deguchi, K., Yamashita, T., Ohta, Y., Morimoto, N., Shang, J., Zhang, X., Liu, N., Ikeda, Y., Matsuura, T., & Abe, K. (2010). In vivo imaging of autophagy in a mouse stroke model. Autophagy, 6(8), 1107–1114. https://doi.org/10.4161/auto.6.8.13427spa
dc.relation.referencesThrift, A. G., Howard, G., Cadilhac, D. A., Howard, V. J., Rothwell, P. M., Thayabaranathan, T., Feigin, V. L., Norrving, B., & Donnan, G. A. (2017). Global stroke statistics: An update of mortality data from countries using a broad code of "cerebrovascular diseases". International journal of stroke: official journal of the International Stroke Society, 12(8), 796–801.spa
dc.relation.referencesTuo, Q. Z., Zhang, S. T., & Lei, P. (2022). Mechanisms of neuronal cell death in ischemic stroke and their therapeutic implications. Medicinal research reviews, 42(1), 259–305. https://doi.org/10.1002/med.21817spa
dc.relation.referencesWang, H. X., Zhang, K., Zhao, L., Tang, J. W., Gao, L. Y., & Wei, Z. P. (2015). Association of liver X receptor α (LXRα) gene polymorphism and ischemic stroke. Genetics and molecular research : GMR, 14(1), 118–122. https://doi.org/10.4238/2015.January.15.14spa
dc.relation.referencesWang, R., Jin, F., & Zhong, H. (2014). A novel experimental hypoxia chamber for cell culture. American journal of cancer research, 4(1), 53–60.spa
dc.relation.referencesWang, Y., & Zhang, H. (2019). Regulation of Autophagy by mTOR Signaling Pathway. Advances in experimental medicine and biology, 1206, 67–83. https://doi.org/10.1007/978-981-15-0602-4_3spa
dc.relation.referencesWen, Y. D., Sheng, R., Zhang, L. S., Han, R., Zhang, X., Zhang, X. D., Han, F., Fukunaga, K., & Qin, Z. H. (2008). Neuronal injury in rat model of permanent focal cerebral ischemia is associated with activation of autophagic and lysosomal pathways. Autophagy, 4(6), 762–769. https://doi.org/10.4161/auto.6412spa
dc.relation.referencesWong, P. M., Feng, Y., Wang, J., Shi, R., & Jiang, X. (2015). Regulation of autophagy by coordinated action of mTORC1 and protein phosphatase 2A. Nature communications, 6, 8048. https://doi.org/10.1038/ncomms9048spa
dc.relation.referencesWright WE, Shay JW. Inexpensive low-oxygen incubators. Nat Protoc. 2006;1(4):2088-90. doi: 10.1038/nprot.2006.374. PMID: 17487199.spa
dc.relation.referencesWu, C. H., Chen, C. C., Lai, C. Y., Hung, T. H., Lin, C. C., Chao, M., & Chen, S. F. (2016). Treatment with TO901317, a synthetic liver X receptor agonist, reduces brain damage and attenuates neuroinflammation in experimental intracerebral hemorrhage. Journal of neuroinflammation, 13(1), 62. https://doi.org/10.1186/s12974-016-0524-8spa
dc.relation.referencesWu, Y., Fan, L., Wang, Y., Ding, J., & Wang, R. (2021). Isorhamnetin Alleviates High Glucose-Aggravated Inflammatory Response and Apoptosis in Oxygen-Glucose Deprivation and Reoxygenation-Induced HT22 Hippocampal Neurons Through Akt/SIRT1/Nrf2/HO-1 Signaling Pathway. Inflammation, 44(5), 1993–2005. https://doi.org/10.1007/s10753-021-01476-1spa
dc.relation.referencesXian, M., , Cai, J., , Zheng, K., , Liu, Q., , Liu, Y., , Lin, H., , Liang, S., , & Wang, S., (2021). Aloe-emodin prevents nerve injury and neuroinflammation caused by ischemic stroke via the PI3K/AKT/mTOR and NF-κB pathway. Food & function, 12(17), 8056–8067. https://doi.org/10.1039/d1fo01144hspa
dc.relation.referencesXiong X, Liang L, Yang Q. (2016), Functions and mechanisms of microglia/macrophages in neuroinflammation and neurogenesis after stroke. Progress in Neurobiology Volume 142, Pages 23-44. https://doi.org/10.1016/j.pneurobio.2016.05.001spa
dc.relation.referencesXiong, Y., Manwani, B., & Fisher, M. (2019). Management of Acute Ischemic Stroke. The American journal of medicine, 132(3), 286–291. https://doi.org/10.1016/j.amjmed.2018.10.019spa
dc.relation.referencesXu, M., & Zhang, H. L. (2011). Death and survival of neuronal and astrocytic cells in ischemic brain injury: a role of autophagy. Acta pharmacologica Sinica, 32(9), 1089–1099. https://doi.org/10.1038/aps.2011.50spa
dc.relation.referencesXu, S., Lu, J., Shao, A., Zhang, J. H., & Zhang, J. (2020). Glial Cells: Role of the Immune Response in Ischemic Stroke. Frontiers in immunology, 11, 294. https://doi.org/10.3389/fimmu.2020.00294spa
dc.relation.referencesYamamoto, A., & Yue, Z. (2014). Autophagy and its normal and pathogenic states in the brain. Annual review of neuroscience, 37, 55–78. https://doi.org/10.1146/annurev-neuro-071013-014149spa
dc.relation.referencesYan X, Zhou R, Ma Z. Autophagy-Cell Survival and Death. Adv Exp Med Biol. 2019;1206:667-696. doi: 10.1007/978-981-15-0602-4_29. PMID: 31777006.spa
dc.relation.referencesYanez, N., Useche, J. N., Bayona, H., Porras, A., & Carrasquilla, G. (2020). Analyses of Mortality and Prevalence of Cerebrovascular Disease in Colombia, South America (2014-2016): A Cross-Sectional and Ecological Study. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, 29(5), 104699. https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.104699spa
dc.relation.referencesYoshii, S. R., & Mizushima, N. (2017). Monitoring and Measuring Autophagy. International Journal of Molecular Sciences, 18(9), 1865. http://doi.org/10.3390/ijms18091865spa
dc.relation.referencesYu, L., Chen, Y., & Tooze, S. A. (2018). Autophagy pathway: Cellular and molecular mechanisms. Autophagy, 14(2), 207–215. doi:10.1080/15548627.2017.1378838 Zelcer, N., & Tontonoz, P. (2006). Liver X receptors as integrators of metabolic and inflammatory signaling. The Journal of clinical investigation, 116(3), 607–614. https://doi.org/10.1172/JCI27883spa
dc.relation.referencesZeng, Z., Zhang, Y., Jiang, W., He, L., & Qu, H. (2020). Modulation of autophagy in traumatic brain injury. Journal of cellular physiology, 235(3), 1973–1985. https://doi.org/10.1002/jcp.29173spa
dc.relation.referencesZhang, Z., Yao, L., Yang, J., Wang, Z., & Du, G. (2018). PI3K/Akt and HIF‑1 signaling pathway in hypoxia‑ischemia (Review). Molecular medicine reports, 18(4), 3547–3554. https://doi.org/10.3892/mmr.2018.9375spa
dc.relation.referencesZhao H, Sapolsky RM, Steinberg GK (2006) Interrupting reperfusion as a stroke therapy: ischemic postconditioning reduces infarct size after focal ischemia in rats. J Cereb Blood Flow Metab 26: 1114–1121spa
dc.relation.referencesZhao, H., Yang, Y., Si, X., Liu, H., & Wang, H. (2022). The Role of Pyroptosis and Autophagy in Ischemia Reperfusion Injury. Biomolecules, 12(7), 1010. https://doi.org/10.3390/biom12071010spa
dc.relation.referencesZhu, C., Wang, X., Xu, F., Bahr, B. A., Shibata, M., Uchiyama, Y., Hagberg, H., & Blomgren, K. (2005). The influence of age on apoptotic and other mechanisms of cell death after cerebral hypoxia-ischemia. Cell death and differentiation, 12(2), 162–176. https://doi.org/10.1038/sj.cdd.4401545spa
dc.relation.referencesZiello, J. E., Jovin, I. S., & Huang, Y. (2007). Hypoxia-Inducible Factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia. The Yale journal of biology and medicine, 80(2), 51–60.spa
dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.licenseAtribución-NoComercial-SinDerivadas 4.0 Internacionalspa
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/spa
dc.subject.ddc610 - Medicina y salud::615 - Farmacología y terapéuticaspa
dc.subject.ddc610 - Medicina y salud::616 - Enfermedadesspa
dc.subject.decsAutofagiaspa
dc.subject.decsAutophagyeng
dc.subject.decsGliomaspa
dc.subject.proposalAutofagiaspa
dc.subject.proposalLXRspa
dc.subject.proposalIsquemia cerebralspa
dc.subject.proposalLC3-IIspa
dc.subject.proposalNeuroprotecciónspa
dc.subject.proposalAutophagyeng
dc.subject.proposalBrain ischemiaeng
dc.subject.proposalNeuroprotectioneng
dc.titlePotencial efecto neuroprotector de los agonistas LXR en la activación de autofagia de células gliales y neuronales sometidas a privación de glucosa y oxígenospa
dc.title.translatedPotential neuroprotective effect of LXR agonists on autophagy activation on glial and neuronal cells subjected to glucose and oxygen deprivationeng
dc.typeTrabajo de grado - Maestríaspa
dc.type.coarhttp://purl.org/coar/resource_type/c_bdccspa
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aaspa
dc.type.contentTextspa
dc.type.driverinfo:eu-repo/semantics/masterThesisspa
dc.type.redcolhttp://purl.org/redcol/resource_type/TMspa
dc.type.versioninfo:eu-repo/semantics/acceptedVersionspa
dcterms.audience.professionaldevelopmentEstudiantesspa
dcterms.audience.professionaldevelopmentInvestigadoresspa
dcterms.audience.professionaldevelopmentMaestrosspa
dcterms.audience.professionaldevelopmentPúblico generalspa
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2spa
oaire.awardtitle“Búsqueda racional de alcaloides isoquinolínicos del género Zanthoxylum (Rutaceae) como posibles agentes neuroprotectores para el tratamiento de la enfermedad de Alzheimer"spa
oaire.fundernameFinanciado por MINCIENCIAS Código 110177758004, convocatoria 777-2017; RC-854 de 2017spa

Archivos

Bloque original

Mostrando 1 - 1 de 1
Cargando...
Miniatura
Nombre:
1023892304.2023.pdf
Tamaño:
1.51 MB
Formato:
Adobe Portable Document Format
Descripción:
Tesis de Maestría en Neurociencias

Bloque de licencias

Mostrando 1 - 1 de 1
No hay miniatura disponible
Nombre:
license.txt
Tamaño:
5.74 KB
Formato:
Item-specific license agreed upon to submission
Descripción: