PEDF attenuates hypoxia-induced apoptosis and necrosis in H9c2 cells by inhibiting p53 mitochondrial translocation via PEDF-R.
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.
Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, 99 Huaihai Road, Xuzhou 221006, Jiangsu Province, China.
Xiaoyu
X
Wang
Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, 99 Huaihai Road, Xuzhou 221006, Jiangsu Province, China.
Yiqian
Y
Zhang
Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, 99 Huaihai Road, Xuzhou 221006, Jiangsu Province, China.
Peng
P
Lu
Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, 99 Huaihai Road, Xuzhou 221006, Jiangsu Province, China.
Hao
H
Zhang
Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, 99 Huaihai Road, Xuzhou 221006, Jiangsu Province, China.
Yufeng
Y
Li
Research Facility Center for Morphology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou 221004, Jiangsu Province, China. Electronic address: dhy@xzmc.edu.cn.
Hongyan
H
Dong
Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, 99 Huaihai Road, Xuzhou 221006, Jiangsu Province, China. Electronic address: zhang_zhongming@xzmc.edu.cn.
Zhongming
Z
Zhang
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D002460:Cell Line; D005136:Eye Proteins / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology*; D009336:Necrosis / Q000473:pathology; D009414:Nerve Growth Factors / Q000378:metabolism*; D051381:Rats; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D024101:Mitochondrial Proteins; D009414:Nerve Growth Factors; D018013:Receptors, Neuropeptide; D015843:Serpins; D016159:Tumor Suppressor Protein p53; D000099174:Pigment Epithelium-Derived Factor; C400531:pigment epithelium-derived factor receptor
Apoptosis; Necrosis; PEDF; PEDF-R; p53 mitochondrial translocation