Cigarette Smoke Extract and Its Cytotoxic Factor Acrolein Inhibit Nitric Oxide Production in Human Vascular Endothelial Cells.
Biol Pharm Bull
; 43(11): 1804-1809, 2020 Nov 01.
Article
in En
| MEDLINE
| ID: mdl-32879145
ABSTRACT
Acrolein (ACR), a highly reactive α,ß-unsaturated aldehyde, is a major cytotoxic factor in nicotine- and tar-free cigarette smoke extract (CSE). There are conflicting results regarding endothelial functions despite the fact that both CSE and ACR cause cellular damage. Several lines of evidence indicate that CSE impairs endothelium-derived nitric oxide (NO)-dependent vasodilation by reducing the activity and protein expression of endothelial NO synthase (eNOS), whereas ACR elicits endothelium-dependent vasorelaxation by increasing the production of NO and expression of eNOS. To clarify whether CSE and its cytotoxic factor ACR cause endothelial dysfunction, this study examined the effects of CSE and ACR on human vascular endothelial EA.hy926 cells. CSE and ACR reduced the phosphorylation of eNOS at serine (Ser)1177 and total expression of eNOS. The CSE- and ACR-induced decrease in the phosphorylation and expression of eNOS was counteracted by glutathione (reduced form), an antioxidant. Basal NO production was inhibited by CSE, ACR, NG-nitro-L-arginine methyl ester (a competitive eNOS inhibitor), and nominally Ca2+-free solution supplemented with BAPTA-AM (a membrane permeable Ca2+ chelator). These results indicate that CSE and ACR increase oxidative stress, and reduce NO production by reducing the activity and total protein level of eNOS.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Nicotiana
/
Acrolein
/
Human Umbilical Vein Endothelial Cells
/
Tobacco Products
/
Cigarette Smoking
Limits:
Humans
Language:
En
Journal:
Biol Pharm Bull
Journal subject:
BIOQUIMICA
/
FARMACOLOGIA
Year:
2020
Document type:
Article