Roles of PTEN-induced putative kinase 1 and dynamin-related protein 1 in transient global ischemia-induced hippocampal neuronal injury

Biochemical and Biophysical Research Communications
Shang-Der ChenYao-Chung Chuang

Abstract

Recent studies showed that increased mitochondrial fission is an early event of cell death during cerebral ischemia and dynamin-related protein 1 (Drp1) plays an important role in mitochondrial fission, which may be regulated by PTEN-induced putative kinase 1 (PINK1), a mitochondrial serine/threonine-protein kinase thought to protect cells from stress-induced mitochondrial dysfunction and regulate mitochondrial fission. However, the roles of PINK1 and Drp1 in hippocampal injury caused by transient global ischemia (TGI) remain unknown. We therefore tested the hypothesis that TGI may induce PINK1 causing downregulation of Drp1 phosphorylation to enhance hippocampal neuronal survival, thus functioning as an endogenous neuroprotective mechanism. We found progressively increased PINK1 expression in the hippocampal CA1 subfield1-48 h following TGI, reaching the maximal level at 4 h. Despite lack of changes in the expression level of total Drp1 and phosphor-Drp1 at Ser637, TGI induced a time-dependent increase of Drp1 phosphorlation at Ser616 that peaked after 24 h. Notably, PINK1-siRNA increased p-Drp1(Ser616) protein level in hippocampal CA1 subfield 24 h after TGI. The PINK1 siRNA also aggravated the TGI-induced oxidative DNA damag...Continue Reading

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Citations

Nov 12, 2015·International Journal of Molecular Sciences·Yao-Chung ChuangShang-Der Chen
Jan 19, 2017·International Journal of Molecular Sciences·Chenxia HuLanjuan Li
Sep 25, 2017·Translational Stroke Research·Nina KlimovaTibor Kristian
Jul 1, 2019·Biological Chemistry·Lena HoffmannCarsten Culmsee
Mar 10, 2017·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·TaeHee Kim, Raghu Vemuganti
Mar 2, 2017·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Eun-A KimSung-Woo Cho
Jan 9, 2021·Frontiers in Aging Neuroscience·Yaqiang LiuChaoyue Meng
Sep 24, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Hong AnXunming Ji

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