Restoration of L-OPA1 alleviates acute ischemic stroke injury in rats via inhibiting neuronal apoptosis and preserving mitochondrial function
| العنوان: | Restoration of L-OPA1 alleviates acute ischemic stroke injury in rats via inhibiting neuronal apoptosis and preserving mitochondrial function |
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| المؤلفون: | Yongxing Lai, Hongbin Chen, Mouwei Zheng, Ji Liu, Xiaodong Pan, Peiqiang Lin, Houwei Du, Nan Liu, Jianhao Chen, Manli Chen, Yixian Zhang, Ronghua Chen |
| المصدر: | Redox Biology Redox Biology, Vol 34, Iss, Pp 101503-(2020) |
| بيانات النشر: | Elsevier, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Mitochondrial DNA, endocrine system, Clinical Biochemistry, Ischemia, Ischemia/reperfusion, Apoptosis, Mitochondrion, medicine.disease_cause, Biochemistry, OPA1, Brain Ischemia, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, lcsh:QH301-705.5, Ischemic Stroke, lcsh:R5-920, Chemistry, Organic Chemistry, Mitochondria function, medicine.disease, eye diseases, Cell biology, Mitochondria, Rats, Stroke, 030104 developmental biology, Glucose, Mitochondrial biogenesis, lcsh:Biology (General), Oxidative stress, Reperfusion Injury, Articles from the Special Issue on Redox Signalling and Cardiovascular Disease, Edited by Christopher Kevil and Yabing Chen, Optic Atrophy 1, lcsh:Medicine (General), Reperfusion injury, 030217 neurology & neurosurgery |
| الوصف: | Background Ischemic stroke can induce changes in mitochondrial morphology and function. As a regulatory gene in mitochondria, optic atrophy 1 (OPA1) plays a pivotal role in the regulation of mitochondrial dynamics and other related functions. However, its roles in cerebral ischemia-related conditions are barely understood. Methods Cultured rat primary cortical neurons were respectively transfected with OPA1-v1ΔS1-encoding and OPA1-v1-encoding lentivirus before exposure to 2-h oxygen-glucose deprivation (OGD) and subsequent reoxygenation (OGD/R). Adult male SD rats received an intracranial injection of AAV-OPA1-v1ΔS1 and were subjected to 90 min of transient middle cerebral artery occlusion (tMCAO) followed by reperfusion. OPA1 expression and function were detected by in vitro and in vivo assays. Results OPA1 was excessively cleaved after cerebral ischemia/reperfusion injury, both in vitro and in vivo. Under OGD/R condition, compared with that of the LV-OPA1-v1-treated group, the expression of OPA1-v1ΔS1 efficiently restored L-OPA1 level and alleviated neuronal death and mitochondrial morphological damage. Meanwhile, the expression of OPA1-v1ΔS1 markedly improved cerebral ischemia/reperfusion-induced motor function damage, attenuated brain infarct volume, neuronal apoptosis, mitochondrial bioenergetics deficits, oxidative stress, and restored the morphology of mitochondrial cristae and mitochondrial length. It also preserved the mitochondrial integrity and reinforced the mtDNA content and expression of mitochondrial biogenesis factors in ischemic rats. Interpretation Our results demonstrate that the stabilization of L-OPA1 protects ischemic brains by reducing neuronal apoptosis and preserving mitochondrial function, suggesting its significance as a promising therapeutic target for stroke prevention and treatment. Graphical abstract Schematic illustration showing that expression of OPA1-v1 ΔS1 reduces neuronal apoptosis and preserves mitochondrial function after cerebral ischemia/reperfusion injury.Image 1 Highlights • Ischemic stroke elicits OPA1 cleavage. • Restoration of L-OPA1 improves motor function recovery and neuronal survival. • Restoration of L-OPA1 maintains mitochondrial morphology and ultrastructure. • Restoration of L-OPA1 ameliorates oxidative stress and bioenergetics deficits. • Restoration of L-OPA1 promotes mitochondrial integrity and biogenesis. |
| اللغة: | English |
| تدمد: | 2213-2317 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::235b35949c0948a7c7b3a0625d5a319cTest http://europepmc.org/articles/PMC7327985Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....235b35949c0948a7c7b3a0625d5a319c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22132317 |
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