title: RTEF-1 protects against oxidative damage induced by H2O2 in human umbilical vein endothelial cells through Klotho activation.
abstract: Oxidative stress is a main risk factor of vascular aging, which may lead to age-associated diseases. Related transcriptional enhancer factor-1 (RTEF-1) has been suggested to regulate many genes expression which are involved in the endothelial angiogenesis and vasodilation. However, whether RTEF-1 has a direct role in anti-oxidation and what specific genes are involved in RTEF-1-driven anti-oxidation have not been elucidated. In this study, we found that overexpressing RTEF-1 in H2O2-treated human umbilical vein endothelial cells decreased senescence-associated-β-galactosidase (SA-β-gal)-positive cells and G0/G1 cells population. The expressions of p53 and p21 were decreased in H2O2-treated RTEF-1 o/e human umbilical vein endothelial cells. However, specific small interfering RNA of RTEF-1 totally reversed the anti-oxidation effect of RTEF-1 and inhibited RTEF-1-induced decreased p53 and p21 expressions. It demonstrated that RTEF-1 could protect cells from H2O2-induced oxidative damage. In addition, we demonstrated that RTEF-1 could up-regulate Klotho gene expression and activate its promoter. Furthermore, Klotho small interfering RNA significantly blocked RTEF-1-driven endothelial cell protection from H2O2-induced oxidative damage and increased p53 and p21 expressions. These results reveal that RTEF-1 is a potential anti-oxidation gene and can prevent H2O2-induced endothelial cell oxidative damage by activating Klotho.
authors.affiliation: Department of Gerontology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Gerontology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Cheng
authors.affiliation: Department of Gerontology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Pan-Ge
authors.initials: PG
authors.lastname: Sun
authors.affiliation: Department of Gerontology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Wu
authors.affiliation: Department of Gerontology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Qin-Qin
authors.initials: QQ
authors.lastname: Wu
authors.affiliation: Department of Gerontology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China doctorpeace74@gmail.com.
authors.forename: Ping
authors.initials: P
authors.lastname: He
mesh_terms: D015153:Blotting, Western; D016922:Cellular Senescence / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005966:Glucuronidase / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D000090265:Klotho Proteins; D009124:Muscle Proteins / Q000502:physiology*; D015689:Oncogene Protein p21(ras) / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D014471:Umbilical Veins / Q000166:cytology* / Q000187:drug effects / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D034741:RNA, Small Interfering; D000091262:TEA Domain Transcription Factors; C486309:TEAD4 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D006861:Hydrogen Peroxide; D005966:Glucuronidase; D000090265:Klotho Proteins; D015689:Oncogene Protein p21(ras)
keywords: Klotho; Related transcriptional enhancer factor-1; human; oxidative stress; senescence; umbilical vein endothelial cells