title: High glucose induces the release of endothelin-1 through the inhibition of hydrogen sulfide production in HUVECs.
abstract: Hydrogen sulfide (H(2)S) has recently been identified as an endogenous gaseous signaling molecule. In the vascular system, the formation of H(2)S is catalyzed by cystathionine γ‑lyase (CSE). Previous studies have demonstrated the protective effects of H(2)S on ischemic injury in various types of tissue. However,, little is known about the role of H(2)S in diabetes-associated vascular diseases. Thus, the aim of the present study was to examine the possible role of H(2)S in high glucose-induced vascular dysfunction, and to explore the underlying mechanisms. Human umbilical vein endothelial cells (HUVECs) were isolated from human umbilical veins. The levels of H(2)S following treatment with various levels of glucose were determined and the secretion of endothelin-1 (ET-1) was measured by ELISA. The mRNA and protein expression of CSE in the HUVECs was determined by real-time RT-PCR and western blot analysis, respectively. Treatment with high glucose (25 mmol/l) for 48 h significantly increased the secretion of ET-1 by HUVECs, with the concomitant suppression of H(2)S production and CSE protein expression. The increase in exogenous H(2)S levels through the administration of sodium hydrosulfide (NaHS) attenuated the high glucose-induced downregulation of CSE protein expression, and significantly inhibited the secretion of ET-1. These results suggest that the downregulation of CSE protein expression and the subsequent decrease in H(2)S production play a role in high glucose-induced vascular dysfunction possibly by increasing the secretion of ET-1 by endothelial cells.
authors.affiliation: Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Guan
authors.affiliation: Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.affiliation: The Second Hospital of Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Yuantao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Youfei
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Yu
authors.affiliation: Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Shunke
authors.initials: S
authors.lastname: Wang
authors.affiliation: Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
mesh_terms: D002460:Cell Line; D003542:Cystathionine gamma-Lyase / Q000235:genetics / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D013440:Sulfides / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D013440:Sulfides; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D005947:Glucose; D006862:Hydrogen Sulfide