Heme oxygenase-1 ameliorates oxidative stress-induced endothelial senescence via regulating endothelial nitric oxide synthase activation and coupling
作者单位：Laboratory of Pharmacology and ToxicologySchool of Pharmaceutical SciencesNational and Local United Engineering Lab of Druggability and New Drugs EvaluationGuangdong Provincial Key Laboratory of New Drug Design and EvaluationSun Yat-sen University
会议名称：《首届东方药理论坛暨2018年全国心脑血管药理学术会议、上海市药理学会第十九届学术年会》
会议日期：2018年
学科分类：100405[医学-卫生毒理学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 10[医学]
关 键 词：endothelial cell endothelial nitric oxide synthase heme oxygenase-1 nitric oxide senescence
摘 要：Aim:Vascular endothelial cells play a pivotal role in regulating hemostasis of the cardiovascular *** senescence of vascular endothelial cells is a leading cause of various cardiovascular *** present study was aimed to evaluate the potential of heme oxygenase-1（HO-1） as a therapeutic target for endothelial ***:Human umbilical vein endothelial cells（HUVECs） were treated with 50μM H O to induce premature ***-1 was up-regulated by the pharmacological inducer hemin or recombinant adenovirus encoding human HO-1,whereas it was knocked down by siRNA or inhibited by inhibitor protoporphyrin IX zinc（Ⅱ）(ZnPP).The treated rats（SHRs） received a single intraperitoneal injection of hemin（10 mg·kg-1 per day） for 10 *** control group（WKYs） and the model group（SHRs） were injected with normal *** 10 days,rats were euthanized and aortas were collected and subjected to staining or Western blot ***-temperature SDS-PAGE was performed for detection of endothelial nitric oxide synthase（eNOS） monomers and *** production of nitric oxide（NO） was measured using the NO-specific fluorescent dye3-Amino,4-aminomethyl-2 ,7 -difluorescein,diacetate（DAF-FM DA）.And living HUVECs were incubated for dye uptake with were 10 μM2,7-Diamino-10-ethyl-9-phenyl-9,10-dihydrophenanthridine（DHE） with cell auto imaging system to detect reactive oxygen species（ROS）.Immunoprecipitation and immunofluorescence were used to study interaction among HO-1,eNOS and ***:Upregulation of HO-1 reversed H O-induced senescence in HUVECs,whereas depletion of HO-1 triggered HUVEC ***,overexpression of HO-1 enhanced the interaction between HO-1 and eNOS,and promoted the interaction between eNOS and its upstream kinase Akt,thus resulting in an enhancement of eNOS phosphorylation at Ser1177 and a subsequent increase of NO ***,HO-1 induction prevented the decrease of eNOS dimer/monomer ratio stimulated by H O via