PEDF attenuates hypoxia-induced apoptosis and necrosis in H9c2 cells by inhibiting p53 mitochondrial translocation via PEDF-R.

Abstract:

:Pigment epithelial-derived factor (PEDF) is a multifunctional secreted glycoprotein, which could protect against hypoxia-induced cell death related to its anti-oxidative effect in cultured cardiomyocytes. However, the pathway mediating this cytoprotective process has not been fully established. Here we confirmed that PEDF bound to pigment epithelial-derived factor receptor (PEDF-R) expressed on the membrane of H9c2 cells. Under hypoxic condition, PEDF increased the ratio of MDM2:p53, so as to inhibited p53 mitochondrial translocation via PEDF-R. As a result, mitochondrial outer membrane permeabilization (MOMP) and mitochondrial permeability transition pore (MPTP) opening were inhibited, meanwhile cleaved caspase-3, PARP and the release of HMGB1 were reduced. Accordingly, apoptosis and necrosis were attenuated simultaneously. We conclude that PEDF-R mediates PEDF attenuates hypoxia-induced apoptosis and necrosis in H9c2 cells by inhibiting p53 mitochondrial translocation.

authors

Wang X,Zhang Y,Lu P,Zhang H,Li Y,Dong H,Zhang Z

doi

10.1016/j.bbrc.2015.08.015

subject

Has Abstract

pub_date

2015-09-25 00:00:00

pages

394-401

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(15)30405-8

journal_volume

465

pub_type

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