缺氧诱导因子-1与缺血性脑卒中的研究进展
Research Progress of Hypoxia-Inducible Factor-1 and Ischemic Stroke
DOI: 10.12677/ACM.2023.13112585, PDF,   
作者: 姚 境:济宁医学院临床医学院,山东 济宁;齐子有*:济宁医学院附属医院神经内科,山东 济宁
关键词: HIF-1缺血性脑卒中氧化应激血管重塑神经炎症HIF-1 Ischemic Stroke Oxidative Stress Angiogenesis Neuroinflammation
摘要: 脑卒中是一种由脑内血管突然破裂或血管堵塞引起的急性脑血管疾病,现已成为我国居民死亡的主要原因之一。脑梗死时,缺氧诱导因子-1 (hypoxia-inducible factor-1, HIF-1)作为缺氧条件下重要的转录调节因子,通过调节糖代谢、血管生成、红细胞生成、细胞存活等多种途径参与脑梗死的病理过程。HIF-1在脑卒中中的调节机制包括能量代谢、氧化应激、血管重塑、神经炎症和细胞坏死、自噬、凋亡。然而,HIF-1在卒中中的作用仍存在争议,具体作用与脑组织缺血时间和缺血程度有关。同时,针对HIF-1与神经系统变性病(如阿尔兹海默症、帕金森病等)之间的关系也有越来越多的研究。基于HIF-1在神经系统疾病中的作用,HIF-1有望成为卒中治疗的潜在靶点,同时解决脑梗死期间对HIF-1何时以及采取何种干预措施的问题将为缺血性脑血管病治疗提供新的策略。
Abstract: Stroke is an acute cerebrovascular disease caused by sudden rupture or blockage of blood vessels in the brain, which has become one of the major causes of death in China. As an important transcrip-tional regulator under hypoxic conditions, hypoxia-inducible factor-1 (HIF-1) is involved in the pathological process of cerebral infarction by regulating glucose metabolism, angiogenesis, eryth-ropoiesis, cell survival, etc. The regulatory mechanisms of HIF-1 in stroke include energy metabo-lism, oxidative stress, vascular remodelling, neuroinflammation, cell necrosis, autophagy and apoptosis. However, the role of HIF-1 in stroke remains controversial, and the specific role is related to the duration and degree of cerebral ischaemia. Meanwhile, the relationship between HIF-1 and neurodegenerative diseases (e.g., Alzheimer’s disease, Parkinson’s disease, etc.) has been increas-ingly studied. Based on its role in neurological diseases, HIF-1 is expected to be a potential target for stroke therapy. Meanwhile, solving the problem of when and what interventions for HIF-1 should be taken at the time of cerebral infarction will provide a new strategy for the treatment of ischaemic cerebrovascular disease.
文章引用:姚境, 齐子有. 缺氧诱导因子-1与缺血性脑卒中的研究进展[J]. 临床医学进展, 2023, 13(11): 18407-18417. https://doi.org/10.12677/ACM.2023.13112585

参考文献

[1] Ganesh, A., Luengo-Fernandez, R., Wharton, R.M., et al. (2017) Time Course of Evolution of Disability and Cause-Specific Mortality after Ischemic Stroke: Implications for Trial Design. Journal of the American Heart Association, 6, e005788. [Google Scholar] [CrossRef
[2] Rhim, T., Lee, D.Y. and Lee, M. (2013) Hypoxia as a Target for Tissue Specific Gene Therapy. Journal of Controlled Release, 172, 484-494. [Google Scholar] [CrossRef] [PubMed]
[3] Yu, M., Pan, Q., Li, W., et al. (2023) Isoliquiritigenin Inhibits Gastric Cancer Growth through Suppressing GLUT4 Mediated Glucose Uptake and Inducing PDHK1/PGC-1α Mediat-ed Energy Metabolic Collapse. Phytomedicine, 121, Article ID: 155045. [Google Scholar] [CrossRef] [PubMed]
[4] Rattner, A., Williams, J. and Nathans, J. (2019) Roles of HIFs and VEGF in Angiogenesis in the Retina and Brain. Journal of Clinical Investigation, 129, 3807-3820. [Google Scholar] [CrossRef
[5] Wu, Y., Zhang, L., Sun, Z., et al. (2023) Preferred Conformation-Guided Discovery of Potent and Orally Active HIF Prolyl Hydroxylase 2 Inhibitors for the Treatment of Anemia. Journal of Me-dicinal Chemistry, 66, 8545-8563. [Google Scholar] [CrossRef] [PubMed]
[6] Qiu, B., Yuan, P., Du, X., et al. (2023) Hypoxia Inducible Factor-1α Is an Important Regulator of Macrophage Biology. Heliyon, 9, e17167. [Google Scholar] [CrossRef] [PubMed]
[7] Chen, W., Jadhav, V., Tang, J., et al. (2008) HIF-1alpha Inhibi-tion Ameliorates Neonatal Brain Injury in a Rat Pup Hypoxic-Ischemic Model. Neurobiology of Disease, 31, 433-441. [Google Scholar] [CrossRef] [PubMed]
[8] Helton, R., Cui, J., Scheel, J.R., et al. (2005) Brain-Specific Knock-Out of Hypoxia-Inducible Factor-1alpha Reduces Rather than Increases Hypoxic-Ischemic Damage. Journal of Neuroscience, 25, 4099-4107. [Google Scholar] [CrossRef
[9] Xie, Y., Shi, X., Sheng, K., et al. (2019) PI3K/Akt Sig-naling Transduction Pathway, Erythropoiesis and Glycolysis in Hypoxia (Review). Molecular Medicine Reports, 19, 783-791. [Google Scholar] [CrossRef] [PubMed]
[10] Wang, G.L., Jiang, B.H., Rue, E.A., et al. (1995) Hypox-ia-Inducible Factor 1 Is a Basic-Helix-Loop-Helix-PAS Heterodimer Regulated by Cellular O2 Tension. Proceedings of the National Academy of Sciences of the United States of America, 92, 5510-5514. [Google Scholar] [CrossRef] [PubMed]
[11] Wu, Y., Li, Z., Mcdonough, M.A., et al. (2021) Inhibition of the Oxygen-Sensing Asparaginyl Hydroxylase Factor Inhibiting Hypoxia-Inducible Factor: A Potential Hypoxia Response Modulating Strategy. Journal of Medicinal Chemistry, 64, 7189-7209. [Google Scholar] [CrossRef] [PubMed]
[12] Masoud, G.N. and Li, W. (2015) HIF-1α Pathway: Role, Reg-ulation and Intervention for Cancer Therapy. Acta Pharmaceutica Sinica B, 5, 378-389. [Google Scholar] [CrossRef] [PubMed]
[13] Semenza, G.L. (2001) HIF-1, O(2), and the 3 PHDs: How Animal Cells Signal Hypoxia to the Nucleus. Cell, 107, 1-3. [Google Scholar] [CrossRef
[14] Wenger, R.H., Stiehl, D.P. and Camenisch, G. (2005) Inte-gration of Oxygen Signaling at the Consensus HRE. Science’s STKE, 2005, re12. [Google Scholar] [CrossRef] [PubMed]
[15] Vangeison, G., Carr, D., Federoff, H.J., et al. (2008) The Good, the Bad, and the Cell Type-Specific Roles of Hypoxia Inducible Factor-1 Alpha in Neurons and Astrocytes. Journal of Neu-roscience, 28, 1988-1993. [Google Scholar] [CrossRef
[16] Hirayama, Y., Anzai, N. and Koizumi, S. (2021) Mecha-nisms Underlying Sensitization of P2X7 Receptors in Astrocytes for Induction of Ischemic Tolerance. Glia, 69, 2100-2110. [Google Scholar] [CrossRef] [PubMed]
[17] Hirayama, Y., Ikeda-Matsuo, Y., Notomi, S., et al. (2015) As-trocyte-Mediated Ischemic Tolerance. Journal of Neuroscience, 35, 3794-3805. [Google Scholar] [CrossRef
[18] Kong, L., Ma, Y., Wang, Z., et al. (2021) Inhibition of Hypoxia Inducible Factor 1 by YC-1 Attenuates Tissue Plasminogen Activator Induced Hemorrhagic Transformation by Suppressing HMGB1/TLR4/NF-κB Mediated Neutrophil Infiltration in Thromboembolic Stroke Rats. International Immunopharmacology, 94, Article ID: 107507. [Google Scholar] [CrossRef] [PubMed]
[19] Bok, S., Kim, Y.-E., Woo, Y., et al. (2017) Hypoxia-Inducible Factor-1α Regulates Microglial Functions Affecting Neuronal Survival in the Acute Phase of Ischemic Stroke in Mice. Oncotarget, 8, 111508-111521. [Google Scholar] [CrossRef] [PubMed]
[20] Mergenthaler, P., Lindauer, U., Dienel, G.A., et al. (2013) Sugar for the Brain: The Role of Glucose in Physiological and Pathological Brain Function. Trends in Neurosciences, 36, 587-597. [Google Scholar] [CrossRef] [PubMed]
[21] Guo, S., Miyake, M., Liu, K.J., et al. (2009) Specific In-hibition of Hypoxia Inducible Factor 1 Exaggerates Cell Injury Induced by in Vitro Ischemia through Deteriorating Cel-lular Redox Environment. Journal of Neurochemistry, 108, 1309-1321. [Google Scholar] [CrossRef] [PubMed]
[22] Quaegebeur, A., Segura, I., Schmieder, R., et al. (2016) Deletion or Inhibition of the Oxygen Sensor PHD1 Protects against Ischemic Stroke via Reprogramming of Neuronal Metabolism. Cell Metabolism, 23, 280-291. [Google Scholar] [CrossRef] [PubMed]
[23] Guo, S., Bragina, O., Xu, Y., et al. (2008) Glucose Up-Regulates HIF-1 Alpha Expression in Primary Cortical Neurons in Response to Hypoxia through Maintaining Cellular Redox Sta-tus. Journal of Neurochemistry, 105, 1849-1860. [Google Scholar] [CrossRef] [PubMed]
[24] Bernaudin, M., Nedelec, A.-S., Divoux, D., et al. (2002) Normobaric Hypoxia Induces Tolerance to Focal Permanent Cerebral Ischemia in Association with an Increased Expres-sion of Hypoxia-Inducible Factor-1 and Its Target Genes, Erythropoietin and VEGF, in the Adult Mouse Brain. Journal of Cerebral Blood Flow & Metabolism, 22, 393-403. [Google Scholar] [CrossRef] [PubMed]
[25] Yan, J., Zhou, B., Taheri, S., et al. (2011) Differential Effects of HIF-1 Inhibition by YC-1 on the Overall Outcome and Blood-Brain Barrier Damage in a Rat Model of Is-chemic Stroke. PLOS ONE, 6, e27798. [Google Scholar] [CrossRef] [PubMed]
[26] Formisano, L., Guida, N., Mascolo, L., et al. (2020) Transcrip-tional and Epigenetic Regulation of ncx1 and ncx3 in the Brain. Cell Calcium, 87, Article ID: 102194. [Google Scholar] [CrossRef] [PubMed]
[27] Valsecchi, V., Pignataro, G., Del Prete, A., et al. (2011) NCX1 Is a Novel Target Gene for Hypoxia-Inducible Factor-1 in Ischemic Brain Preconditioning. Stroke, 42, 754-763. [Google Scholar] [CrossRef
[28] Jin, W., Zhao, J., Yang, E., et al. (2022) Neuronal STAT3/HIF-1α/PTRF Axis-Mediated Bioenergetic Disturbance Exacerbates Cerebral Ischemia-Reperfusion Injury via PLA2G4A. Theranostics, 12, 3196-3216. [Google Scholar] [CrossRef] [PubMed]
[29] El Kossi, M.M. and Zakhary, M.M. (2000) Oxidative Stress in the Context of Acute Cerebrovascular Stroke. Stroke, 31, 1889-1892. [Google Scholar] [CrossRef
[30] Wu, L.-Y., He, Y.-L. and Zhu, L.-L. (2018) Possible Role of PHD Inhibitors as Hypoxia-Mimicking Agents in the Maintenance of Neural Stem Cells’ Self-Renewal Properties. Frontiers in Cell and Developmental Biology, 6, Article No. 169. [Google Scholar] [CrossRef] [PubMed]
[31] Guzy, R.D., Hoyos, B., Robin, E., et al. (2005) Mitochondrial Com-plex III Is Required for Hypoxia-Induced ROS Production and Cellular Oxygen Sensing. Cell Metabolism, 1, 401-408. [Google Scholar] [CrossRef] [PubMed]
[32] Lluis, J.M., Buricchi, F., Chiarugi, P., et al. (2007) Dual Role of Mitochondrial Reactive Oxygen Species in Hypoxia Signaling: Activation of Nuclear Factor-{kappa}B via c-SRC and Oxidant-Dependent Cell Death. Cancer Research, 67, 7368-7377. [Google Scholar] [CrossRef
[33] Matrone, C., Pignataro, G., Molinaro, P., et al. (2004) HIF-1alpha Reveals a Binding Activity to the Promoter of iNOS Gene after Permanent Middle Cerebral Artery Occlusion. Journal of Neurochemistry, 90, 368-378. [Google Scholar] [CrossRef] [PubMed]
[34] Hewett, S.J., Muir, J.K., Lobner, D., et al. (1996) Potentia-tion of Oxygen-Glucose Deprivation-Induced Neuronal Death after Induction of iNOS. Stroke, 27, 1586-1591. [Google Scholar] [CrossRef
[35] Fang, L.Q., Xu, H., Sun, Y., et al. (2012) Induction of Inducible Nitric Oxide Synthase by Isoflurane Post-Conditioning via Hypoxia Inducible Factor-1α during Tolerance against Is-chemic Neuronal Injury. Brain Research, 1451, 1-9. [Google Scholar] [CrossRef] [PubMed]
[36] Semenza, G.L. (2014) Oxygen Sensing, Hypoxia-Inducible Factors, and Disease Pathophysiology. Annual Review of Pathology, 9, 47-71. [Google Scholar] [CrossRef] [PubMed]
[37] Sun, P., Zhang, K., Hassan, S.H., et al. (2020) Endo-thelium-Targeted Deletion of microRNA-15a/16-1 Promotes Poststroke Angiogenesis and Improves Long-Term Neuro-logical Recovery. Circulation Research, 126, 1040-1057. [Google Scholar] [CrossRef
[38] Abdel-Latif, R.G., Rifaai, R.A. and Amin, E.F. (2020) Empagliflozin Alleviates Neuronal Apoptosis Induced by Cerebral Ischemia/Reperfusion Injury through HIF-1α/VEGF Signaling Pathway. Archives of Pharmacal Research, 43, 514-525. [Google Scholar] [CrossRef] [PubMed]
[39] Daneman, R., Zhou, L., Kebede, A.A., et al. (2010) Pericytes Are Required for Blood-Brain Barrier Integrity during Embryogenesis. Nature, 468, 562-566. [Google Scholar] [CrossRef] [PubMed]
[40] Tsao, C.-C., Baumann, J., Huang, S.-F., et al. (2021) Pericyte Hypox-ia-Inducible Factor-1 (HIF-1) Drives Blood-Brain Barrier Disruption and Impacts Acute Ischemic Stroke Outcome. An-giogenesis, 24, 823-842. [Google Scholar] [CrossRef] [PubMed]
[41] Allen, N.J. and Lyons, D.A. (2018) Glia as Architects of Central Nervous System Formation and Function. Science, 362, 181-185. [Google Scholar] [CrossRef] [PubMed]
[42] Borst, K., Dumas, A.A. and Prinz, M. (2021) Microglia: Immune and Non-Immune Functions. Immunity, 54, 2194-2208. [Google Scholar] [CrossRef] [PubMed]
[43] Freeman, M.R. (2010) Specification and Morphogenesis of Astrocytes. Science, 330, 774-778. [Google Scholar] [CrossRef] [PubMed]
[44] Yates, D. (2017) Glia: A Toxic Reaction. Nature Reviews Neurosci-ence, 18, 130. [Google Scholar] [CrossRef] [PubMed]
[45] Chen, C., Ostrowski, R.P., Zhou, C., et al. (2010) Sup-pression of Hypoxia-Inducible Factor-1alpha and Its Downstream Genes Reduces Acute Hyperglycemia-Enhanced Hemorrhagic Transformation in a Rat Model of Cerebral Ischemia. Journal of Neuroscience Research, 88, 2046-2055. [Google Scholar] [CrossRef] [PubMed]
[46] Mojsilovic-Petrovic, J., Callaghan, D., Cui, H., et al. (2007) Hypox-ia-Inducible Factor-1 (HIF-1) Is Involved in the Regulation of Hypoxia-Stimulated Expression of Monocyte Chemoat-tractant Protein-1 (MCP-1/CCL2) and MCP-5 (Ccl12) in Astrocytes. Journal of Neuroinflammation, 4, Article No. 12. [Google Scholar] [CrossRef] [PubMed]
[47] Tsan, M.-F. (2006) Toll-Like Receptors, Inflammation and Cancer. Seminars in Cancer Biology, 16, 32-37. [Google Scholar] [CrossRef] [PubMed]
[48] Fang, H., Wang, P.F., Zhou, Y., et al. (2013) Toll-Like Re-ceptor 4 Signaling in Intracerebral Hemorrhage-Induced Inflammation and Injury. Journal of Neuroinflammation, 10, Ar-ticle No. 794. [Google Scholar] [CrossRef] [PubMed]
[49] Rius, J., Guma, M., Schachtrup, C., et al. (2008) NF-kappaB Links Innate Immunity to the Hypoxic Response through Transcriptional Regulation of HIF-1alpha. Nature, 453, 807-811. [Google Scholar] [CrossRef] [PubMed]
[50] Yao, L., Kan, E.M., Lu, J., et al. (2013) Toll-Like Receptor 4 Mediates Microglial Activation and Production of Inflammatory Mediators in Neonatal Rat Brain Following Hypoxia: Role of TLR4 in Hypoxic Microglia. Journal of Neuroinflammation, 10, Article No. 23. [Google Scholar] [CrossRef] [PubMed]
[51] An, P., Xie, J., Qiu, S., et al. (2019) Hispidulin Exhibits Neuropro-tective Activities against Cerebral Ischemia Reperfusion Injury through Suppressing NLRP3-Mediated Pyroptosis. Life Sciences, 232, Article ID: 116599. [Google Scholar] [CrossRef] [PubMed]
[52] Yuan, D., Guan, S., Wang, Z., et al. (2021) HIF-1α Aggravated Traumatic Brain Injury by NLRP3 Inflammasome-Mediated Pyroptosis and Activation of Microglia. Journal of Chemical Neuroanatomy, 116, Article ID: 101994. [Google Scholar] [CrossRef] [PubMed]
[53] Taylor, C.T. and Scholz, C.C. (2022) The Effect of HIF on Metabolism and Immunity. Nature Reviews Nephrology, 18, 573-587. [Google Scholar] [CrossRef] [PubMed]
[54] Giulian, D. (1993) Reactive Glia as Rivals in Regulating Neu-ronal Survival. Glia, 7, 102-110. [Google Scholar] [CrossRef] [PubMed]
[55] Liddelow, S.A., Guttenplan, K.A., Clarke, L.E., et al. (2017) Neuro-toxic Reactive Astrocytes Are Induced by Activated Microglia. Nature, 541, 481-487. [Google Scholar] [CrossRef] [PubMed]
[56] Pollay, M. (2010) The Function and Structure of the Cerebrospinal Fluid Outflow System. Cerebrospinal Fluid Research, 7, Article No. 9. [Google Scholar] [CrossRef] [PubMed]
[57] Rasmussen, M.K., Mestre, H. and Nedergaard, M. (2018) The Glym-phatic Pathway in Neurological Disorders. The Lancet Neurology, 17, 1016-1024. [Google Scholar] [CrossRef
[58] Iliff, J.J., Wang, M., Liao, Y., et al. (2012) A Paravascular Pathway Facilitates CSF Flow through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β. Science Translational Medicine, 4, 147ra11. [Google Scholar] [CrossRef] [PubMed]
[59] Mestre, H., Hablitz, L.M., Xavier, A.L., et al. (2018) Aqua-porin-4-Dependent Glymphatic Solute Transport in the Rodent Brain. Elife, 7, e40070. [Google Scholar] [CrossRef
[60] Xiong, A., Li, J., Xiong, R., et al. (2022) Inhibition of HIF-1α-AQP4 Axis Ameliorates Brain Edema and Neurological Functional Deficits in a Rat Controlled Cortical Injury (CCI) Model. Scientific Reports, 12, Article No. 2701. [Google Scholar] [CrossRef] [PubMed]
[61] Leng, F. and Edison, P. (2021) Neuroinflammation and Micro-glial Activation in Alzheimer Disease: Where Do We Go from Here? Nature Reviews Neurology, 17, 157-172. [Google Scholar] [CrossRef] [PubMed]
[62] Yun, S.P., Kam, T.-I., Panicker, N., et al. (2018) Block of A1 Astrocyte Conversion by Microglia Is Neuroprotective in Models of Parkinson’s Disease. Nature Medicine, 24, 931-938. [Google Scholar] [CrossRef] [PubMed]
[63] Vidal-Itriago, A., Radford, R.A.W., Aramideh, J.A., et al. (2022) Microglia Morphophysiological Diversity and Its Implications for the CNS. Frontiers in Immunology, 13, Article ID: 997786. [Google Scholar] [CrossRef] [PubMed]
[64] Ikeda, T., Xia, X.Y., Xia, Y.X., et al. (2000) Glial Cell Line-Derived Neurotrophic Factor Protects against Ischemia/Hypoxia-Induced Brain Injury in Neonatal Rat. Acta Neu-ropathologica, 100, 161-167. [Google Scholar] [CrossRef] [PubMed]
[65] Te Boekhorst, V., Jiang, L., Mählen, M., et al. (2022) Calpain-2 Reg-ulates Hypoxia/HIF-Induced Plasticity toward Amoeboid Cancer Cell Migration and Metastasis. Current Biology, 32, 412-427.E8. [Google Scholar] [CrossRef] [PubMed]
[66] Deng, H., Tian, X., Sun, H., et al. (2022) Calpain-1 Mediates Vas-cular Remodelling and Fibrosis via HIF-1α in Hypoxia-Induced Pulmonary Hypertension. Journal of Cellular and Mo-lecular Medicine, 26, 2819-2830. [Google Scholar] [CrossRef] [PubMed]
[67] Yeh, S.-H., Ou, L.-C., Gean, P.-W., et al. (2011) Selective Inhibition of Early—but Not Late—Expressed HIF-1α Is Neuroprotective in Rats after Focal Ischemic Brain Damage. Brain Patholo-gy, 21, 249-262. [Google Scholar] [CrossRef] [PubMed]
[68] Peña-Blanco, A. and García-Sáez, A.J. (2018) Bax, Bak and Beyond-Mitochondrial Performance in Apoptosis. The FEBS Journal, 285, 416-431. [Google Scholar] [CrossRef] [PubMed]
[69] Chen, D., Li, M., Luo, J., et al. (2003) Direct Interactions between HIF-1 Alpha and Mdm2 Modulate p53 Function. Journal of Biological Chemistry, 278, 13595-13598. [Google Scholar] [CrossRef
[70] Li, J., Tao, T., Xu, J., et al. (2020) HIF-1α Attenuates Neuronal Apoptosis by Upregulating EPO Expression Following Cerebral Ischemia-Reperfusion Injury in a Rat MCAO Model. International Journal of Molecular Medicine, 45, 1027-1036. [Google Scholar] [CrossRef] [PubMed]
[71] Garibotto, G., Gurreri, G., Robaudo, C., et al. (1993) Erythropoietin Treatment and Amino Acid Metabolism in Hemodialysis Patients. Nephron, 65, 533-536. [Google Scholar] [CrossRef] [PubMed]
[72] Kang, Y.-J., Digicaylioglu, M., Russo, R., et al. (2010) Erythropoietin plus Insulin-Like Growth Factor-I Protects against Neuronal Damage in a Murine Model of Human Immunodeficiency Vi-rus-Associated Neurocognitive Disorders. Annals of Neurology, 68, 342-352. [Google Scholar] [CrossRef] [PubMed]
[73] Naama, M. and Bel, S. (2023) Autophagy-ER Stress Crosstalk Controls Mucus Secretion and Susceptibility to Gut Inflammation. Autophagy, 19, 3014-3016. [Google Scholar] [CrossRef] [PubMed]
[74] Jaeger, P.A. and Wyss-Coray, T. (2009) All-You-Can-Eat: Autophagy in Neurodegeneration and Neuroprotection. Molecular Neurodegeneration, 4, Article No. 16. [Google Scholar] [CrossRef] [PubMed]
[75] Lu, N., Li, X., Tan, R., et al. (2018) HIF-1α/Beclin1-Mediated Au-tophagy Is Involved in Neuroprotection Induced by Hypoxic Preconditioning. Journal of Molecular Neuroscience, 66, 238-250. [Google Scholar] [CrossRef] [PubMed]
[76] Niu, G., Zhu, D., Zhang, X., et al. (2018) Role of Hypox-ia-Inducible Factors 1α (HIF1α) in SH-SY5Y Cell Autophagy Induced by Oxygen-Glucose Deprivation. Medical Sci-ence Monitor, 24, 2758-2766. [Google Scholar] [CrossRef
[77] Daskalaki, I., Gkikas, I. and Tavernarakis, N. (2018) Hypoxia and Se-lective Autophagy in Cancer Development and Therapy. Frontiers in Cell and Developmental Biology, 6, Article No. 104. [Google Scholar] [CrossRef] [PubMed]
[78] Wang, Y., Dong, X.-X., Cao, Y., et al. (2009) p53 Induction Con-tributes to Excitotoxic Neuronal Death in Rat Striatum through Apoptotic and Autophagic Mechanisms. European Jour-nal of Neuroscience, 30, 2258-2270. [Google Scholar] [CrossRef] [PubMed]
[79] Zhang, H., Bosch-Marce, M., Shimoda, L.A., et al. (2008) Mitochondrial Autophagy Is an HIF-1-Dependent Adaptive Metabolic Response to Hypoxia. Journal of Biological Chemistry, 283, 10892-10903. [Google Scholar] [CrossRef