title: PEDF and PEDF-derived peptide 44mer inhibit oxygen-glucose deprivation-induced oxidative stress through upregulating PPARγ via PEDF-R in H9c2 cells.
abstract: Pigment epithelial-derived factor (PEDF) is a glycoprotein with broad biological activities including inhibiting oxygen-glucose deprivation(OGD)-induced cardiomyocytes apoptosis through its anti-oxidative properties. PEDF derived peptide-44mer shows similar cytoprotective effect to PEDF. However, the molecular mechanisms mediating cardiomyocytes apoptosis have not been fully established. Here we found that PEDF and 44mer decreased the content of ROS. This content was abolished by either PEDF-R small interfering RNA (siRNA) or PPARγ antagonist. The level of Lysophosphatidic acid (LPA) and phospholipase A2 (PLA2) was observed as drawn from the ELISA assays. PEDF and 44mer sequentially induced PPARγ expression was observed both in qPCR and Western blot assays. The level of LPA and PLA2 and PPARγ expression increased by PEDF and 44mer was significantly attenuated by PEDF-R siRNA. However, PEDF and 44mer inhibited the H9c2 cells and cultured neonatal rat myocardial cells apoptosis rate. On the other hand, TUNEL assay and cleavage of procaspase-3 showed that PEDF-R siRNA or PPARγ antagonist increased the apoptosis again. We conclude that under OGD condition, PEDF and 44mer reduce H9c2 cells apoptosis and inhibit OGD-induced oxidative stress via its receptor PEDF-R and the PPARγ signaling pathway.
authors.affiliation: Research Facility Center for Morphology, 209 Tong shan Road, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhuang
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, 99 West Huaihai Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, 99 West Huaihai Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, 99 West Huaihai Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, 99 West Huaihai Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Tengteng
authors.initials: T
authors.lastname: Wei
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, 99 West Huaihai Road, Xuzhou, Jiangsu, 221002, China.
authors.forename: Huazhu
authors.initials: H
authors.lastname: Cui
authors.affiliation: Research Facility Center for Morphology, 209 Tong shan Road, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Research Center for Biochemistry and Molecular Biology and Provincial Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, China.
authors.forename: Qiuhua
authors.initials: Q
authors.lastname: Guan
authors.affiliation: Research Facility Center for Morphology, 209 Tong shan Road, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, China. Electronic address: dhy@xzmc.edu.cn.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, 99 West Huaihai Road, Xuzhou, Jiangsu, 221002, China. Electronic address: zhang_zhongming@xzmc.edu.cn.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D002460:Cell Line; D005136:Eye Proteins / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008970:Molecular Weight; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D005947:Glucose; D009414:Nerve Growth Factors; D010100:Oxygen; D047495:PPAR gamma; D010455:Peptides; D018013:Receptors, Neuropeptide; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor; C400531:pigment epithelium-derived factor receptor
keywords: Apoptosis; Oxygen–glucose deprivation; PEDF; PEDF-R; PPARγ