Proteomic analysis of oxidative stress response in human umbilical vein endothelial cells (HUVECs): role of heme oxygenase 1 (HMOX1) in hypoxanthine-induced oxidative stress in HUVECs.
机构：[1]Department of Infertility and Sexual Medicine, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China中山大学附属第三医院[2]Department of Urology, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China[3]Guangxi University of Chinese Medicine, Nanning 530200, China[4]Department of Urology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China中山大学附属第三医院[5]Department of Urology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China[6]Guangdong Provincial Key Laboratory of Liver Disease, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China中山大学附属第三医院
Erectile dysfunction (ED) is a well-known complication of diabetes, affecting up to 75% of diabetic men. Although the etiology of diabetic ED is multifactorial, endothelial dysfunction is considered to be a pillar of its pathophysiology. Endothelial dysfunction is caused by the harmful effects of high glucose levels and increased oxidative stress on the endothelial cells that comprise the vascular endothelium. The aim of this study was to identify the proteomic changes caused by high glucose-induced oxidative stress and explore the role of heme oxygenase 1 (HMOX1) in it.
The cellular proteomic response to hypoxanthine-induced oxidative stress in human umbilical vein endothelial cells (HUVECs) was analyzed by isobaric tags for relative and absolute quantitation (iTRAQ) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins (DEPs) were analyzed through Network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Further validation assays was performed to validate the role of HMOX1.
The results showed that 66 and 76 DEPs were markedly upregulated and downregulated, respectively, for HUVECs oxidative stress. Among these proteins, we verified eight dysregulated genes by quantitative reverse transcription PCR, including nucleolin (NCL), X-ray repair cross-complementing protein 6 (XRCC6), ubiquinol-cytochrome C reductase binding protein (UQCRB), non-POU domain containing octamer binding (NONO), heme oxygenase 1 (HMOX1), nucleobindin 1 (NUCB1), DEK, and chromatin target of prmt1 (CHTOP). Further, using overexpression and genetic knockdown approaches, we found that HMOX1 was critical for the oxidative stress response in HUVECs.
We found that HMOX1 was closely related to the oxidative stress response induced by hypoxanthine. To the best of our knowledge, this study is the first overview of the responses of HUVECs to oxidative stress. The findings will contribute to analyses of the detailed molecular mechanisms involved in the pathogenesis of endothelial dysfunction and related molecular mechanisms in ED patients.
2020 Translational Andrology and Urology. All rights reserved.
基金：
National Natural Science Foundation of China (grant No. 81871158， 81370705 and 81571432).
第一作者机构：[1]Department of Infertility and Sexual Medicine, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Infertility and Sexual Medicine, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China[5]Department of Urology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China[6]Guangdong Provincial Key Laboratory of Liver Disease, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China[*1]Department of Infertility and Sexual Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou 510630, China[*2]Guangdong Provincial Key Laboratory of Liver Disease, the Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, China[*3]Department of Urology, The Fifth Affiliated Hospital of Sun Yat‐sen University, Zhuhai 519000, China
推荐引用方式(GB/T 7714)：
Zhu Pei,Qi Tao,Huang Zhan-Sen,et al.Proteomic analysis of oxidative stress response in human umbilical vein endothelial cells (HUVECs): role of heme oxygenase 1 (HMOX1) in hypoxanthine-induced oxidative stress in HUVECs.[J].TRANSLATIONAL ANDROLOGY AND UROLOGY.2020,9(2):218-+.doi:10.21037/tau.2020.03.11.
APA：
Zhu Pei,Qi Tao,Huang Zhan-Sen,Li Hao,Wang Bo...&Chen Jun.(2020).Proteomic analysis of oxidative stress response in human umbilical vein endothelial cells (HUVECs): role of heme oxygenase 1 (HMOX1) in hypoxanthine-induced oxidative stress in HUVECs..TRANSLATIONAL ANDROLOGY AND UROLOGY,9,(2)
MLA：
Zhu Pei,et al."Proteomic analysis of oxidative stress response in human umbilical vein endothelial cells (HUVECs): role of heme oxygenase 1 (HMOX1) in hypoxanthine-induced oxidative stress in HUVECs.".TRANSLATIONAL ANDROLOGY AND UROLOGY 9..2(2020):218-+
