Ischemic postconditioning confers cerebroprotection by stabilizing VDACs after brain ischemia.

Cell death & disease (2018-10-12)
Gui-Ying Yao, Qian Zhu, Jing Xia, Feng-Jiao Chen, Ming Huang, Jing Liu, Ting-Ting Zhou, Jian-Feng Wei, Gui-Yun Cui, Kui-Yang Zheng, Xiao-Yu Hou
ABSTRAKT

Ischemic postconditioning provides robust neuroprotection, therefore, determining the molecular events may provide promising targets for stroke treatment. Here, we showed that the expression of functional mitochondrial voltage-dependent anion channel proteins (VDAC1, VDAC2, and VDAC3) reduced in rat vulnerable hippocampal CA1 subfield after global ischemia. Ischemic postconditioning restored VDACs to physiological levels. Stabilized VDACs contributed to the benefits of postconditioning. VDAC1 was required for maintaining neuronal Ca2+ buffering capacity. We found that microRNA-7 (miR-7) was responsible for postischemic decline of VDAC1 and VDAC3. Notably, miR-7 was more highly expressed in the peripheral blood of patients with acute ischemic stroke compared to healthy controls. Inhibition of miR-7 attenuated neuronal loss and ATP decline after global ischemia, but also diminished the infarct volume with improved neurological functions after focal ischemia. Thus, ischemic postconditioning protects against mitochondrial damage by stabilizing VDACs. MiR-7 may be a potential therapeutic target for ischemic stroke.

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Sigma-Aldrich
Anti-VDAC1 Antibody, clone N152B/23, clone N152B/23, from mouse
Sigma-Aldrich
Anti-VDAC3 antibody produced in rabbit, affinity isolated antibody