title: Hydrogen sulfide suppresses high glucose-induced expression of intercellular adhesion molecule-1 in endothelial cells.
abstract: Hydrogen sulfide (H₂S) is a newly identified endogenous gasotransmitter that has been implicated in the pathophysiology of several biologic systems. However, the role of H₂S in the pathogenesis of diabetic vascular injury remains unclear. The aims of this study were to determine the effect of H₂S on the high glucose (HG)-induced expression of intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells and to explore the possible underlying mechanisms. Human umbilical vein endothelial cells were exposed either to a normal concentration of D-glucose (5.5 mmol/L) or to HG (16.7 mmol/L) in the absence or presence of NaHS for the indicated periods. The ICAM-1 protein and messenger RNA (mRNA) levels were analyzed by Western blotting and real-time reverse transcriptase-polymerase chain reaction, respectively. Exposure to HG for 48 or 72 hours significantly increased ICAM-1 expression at both the protein and mRNA levels, and these increases correlated with increases in both the production of intracellular reactive oxygen species and the activation of nuclear factor-κB. Pretreatment with NaHS inhibited HG-induced ICAM-1 expression at both the protein and mRNA levels and resulted in a reduction in the intracellular reactive oxygen species level and the suppression of nuclear factor-κB activity. NaHS also inhibited tumor necrosis factor-α-induced ICAM-1 protein expression, which was similar to the effect of antioxidant N-acetyl-L-cysteine. These findings indicate that H₂S might protect against HG-induced vascular damage by down-regulating ICAM-1 expression in endothelial cells.
authors.affiliation: *Provincial Hospital affiliated to Shandong University, Jinan, China; †Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, China; ‡Department of Cell Biology, Shandong University, Jinan, China; and §Department of Endocrinology, The Second Hospital of Shandong University, Jinan, China.
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Guan
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.forename: Jicui
authors.initials: J
authors.lastname: Chen
authors.forename: Yuantao
authors.initials: Y
authors.lastname: Liu
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Yu
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Jiajun
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003925:Diabetic Angiopathies / Q000097:blood / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D024202:Electrophoretic Mobility Shift Assay; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D006943:Hyperglycemia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D016328:NF-kappa B / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D051996:Transcription Factor RelA / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; C573420:ICAM1 protein, human; D016328:NF-kappa B; C498143:RELA protein, human; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D006862:Hydrogen Sulfide