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Cigarette smoke extract causes endothelial nitric oxide synthase dysfunction through S‐glutathionylation
Author(s) -
Abdelghany Tamer M,
Hemann Craig,
ElSherbiny Gamal A,
ElMahdy Mohamed A,
Zweier Jay L
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.890.11
Subject(s) - enos , glutathione , nitric oxide , endothelial dysfunction , nitric oxide synthase type iii , chemistry , nitric oxide synthase , medicine , endocrinology , biochemistry , enzyme
Dysfunction of endothelial nitric oxide synthase (eNOS) occurs in a wide range of cardiovascular disease and has been linked to cigarette smoking (CS)‐induced endothelial dysfunction (ED). Glutathionylation has recently been reported as a novel mechanism for eNOS uncoupling in ED. However, the role of eNOS glutathionylation in CS‐induced ED remains to be investigated. Bovine aortic endothelial cells (BAECs) were exposed to cigarette smoke extract (CSE) at different concentrations for two hours. Nitric oxide (NO) production, superoxide (O 2 • − ) generation and glutathione level were assessed. Formation of glutathionylated proteins was determined in the lysate or after pull down of eNOS following exposure to CSE with or without N‐acetyl cysteine (NAC). We show that exposure of BAECs to CSE decreased NO production with a concomitant increase in O 2 •− generation and depletion of cellular reduced glutathione. More importantly, formation of protein glutathionylation was significantly higher in CSE‐exposed cells. Pre‐incubation with NAC enhanced eNOS function, decreased eNOS glutathionylation and increased reduced glutathione in CSE‐exposed cells. Our data indicate that CS‐induced ED could be explained, at least in part, through eNOS glutathionylation. The role of CS‐induced eNOS glutathionylation, in the process of ED, and reversal of such modifications in animal models or human subjects warrants further investigation.(NIH# HL38324 to JLZ; and Egyptian government)