1. Heat Shock Protein B8 (HSPB8) Reduces Oxygen-Glucose Deprivation/Reperfusion Injury via the Induction of Mitophagy.
- Author
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Li F, Tan J, Zhou F, Hu Z, and Yang B
- Subjects
- Animals, Brain Ischemia etiology, Brain Ischemia pathology, Cell Hypoxia, Cell Line, Electron Transport Complex IV genetics, Electron Transport Complex IV metabolism, HSP20 Heat-Shock Proteins antagonists & inhibitors, HSP20 Heat-Shock Proteins genetics, Heat-Shock Proteins, Infarction, Middle Cerebral Artery complications, Male, Membrane Transport Proteins genetics, Membrane Transport Proteins metabolism, Mice, Mice, Inbred C57BL, Microtubule-Associated Proteins metabolism, Mitochondria metabolism, Mitochondrial Precursor Protein Import Complex Proteins, Molecular Chaperones, Muscle Proteins antagonists & inhibitors, Muscle Proteins genetics, RNA Interference, RNA, Small Interfering metabolism, Receptors, Cell Surface genetics, Receptors, Cell Surface metabolism, Reperfusion Injury pathology, Transcription Factor TFIIH, Transcription Factors metabolism, Glucose metabolism, HSP20 Heat-Shock Proteins metabolism, Mitophagy, Muscle Proteins metabolism
- Abstract
Background/aims: We have reported the neuroprotective properties of Heat shock protein B8(HSPB8) against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury by inhibiting the mitochondrial apoptotic pathway. However, the exact underlying mechanism of its protective effect on mitochondrial function remains unknown. Here we examined whether the beneficial effect of HSPB8 on OGD/R-induced cell death is associated with mitophagy in mouse neuroblastoma Neuro2a (N2a) cells., Methods: Using the mouse transient middle cerebral artery occlusion (tMCAO) model and mouse neuroblastoma Neuro2a (N2a) cell cultures subjected to OGD/R, we employed western-blot, RT-PCR and immunostaining to analyze the change of expression pattern of HSPB8 and mitophagic flux after brain I/R both in vivo and in vitro. Moreover, via overexpressing HSPB8 or knocking down HSPB8 expression with siRNA in N2a cell, we evaluated the effect of HSPB8 on mitochondrial function during OGD/R. The impact of HSPB8 on mitophagic pathway was also assessed. Finally, mitotophagy inhibitors (CQ and Mdivi-1) were adopted to verify the involvement of mitophagy in HSPB8- induced neuroprotection., Results: HSPB8 could be up-regulated by brain I/R both in vivo and in vitro. Mitophagy enhancement coincided with induction of HSPB8 during I/R. Overexpression of HSPB8 reinforced I/R-induced mitophagy in OGD/R-treated mouse N2a cells and HSPB8 silence suppressed mitophagy process. Inhibition of mitophagy compromised neuroprotection conferred by HSPB8 overexpression., Conclusions: HSPB8 promoted OGD/R-induced mitophagy, which restored the mitochondrial function and contributed to the decrease in cell apoptosis after OGD/R. Therefore, HSPB8 could be a favorable neuroprotective agent for cerebral I/R related disorders., (© 2018 The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2018
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