Facilitated nitration and oxidation of LDL in cigarette smokers.
BACKGROUND
Cigarette smoking increases the risk of developing atherosclerosis and ischaemic heart disease. Smoking-induced oxidative stress is considered to favour oxidation of low-density lipoprotein (LDL) and subsequently promotes the atherogenic process. We investigated whether peroxynitrite, a reaction product of cigarette smoke, is involved in facilitated oxidation of LDL in smokers.


METHODS
Plasma LDL was obtained from 10 healthy asymptomatic cigarette smokers and 10 healthy nonsmokers. The state of enhanced oxidative stress in the plasma was assessed by LDL subfraction assay using anion-exchange high-performance liquid chromatography (AE-HPLC) and measurements of thiobarbituric acid-reactive substances (TBARS), 8-hydroxydeoxyguanosine (8-OHdG), vitamin E, 3-nitrotyrosine and 3-chlorotyrosine.


RESULTS
Smokers showed a significantly higher level of TBARS and 8-OHdG as well as a significantly lower level of vitamin E than nonsmokers, even after stopping smoking for 10 h or more. The LDL subfraction assay demonstrated an increase in oxidatively modified LDL, as expressed by lower levels of LDL1 and higher levels of LDL2. The 3-nitrotyrosine levels in apolipoprotein B in LDL were significantly higher in smokers than nonsmokers, while the 3-chlorotyrosine levels remained unchanged. In addition, these changes observed in the smokers were further accelerated within 30 min after resumption of cigarette smoking when compared with the levels before smoking resumption.


CONCLUSIONS
The present study suggests that peroxynitrite plays a significant role in oxidative modification of plasma LDL induced by cigarette smoking.
Yamaguchi
Y
Y
Mukogawa Women's University, 11-68 Koshien Kyuban-cho, Nishinomiya 663-8179, Japan. yusan@mwu.mukogawa-u.ac.jp
Haginaka
J
J
Morimoto
S
S
Fujioka
Y
Y
Kunitomo
M
M
D000080242:8-Hydroxy-2'-Deoxyguanosine / Q000031:analogs & derivatives; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000097:blood; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D030421:Peroxynitrous Acid / Q000502:physiology*; D012907:Smoking / Q000097:blood*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood*; D014810:Vitamin E / Q000097:blood
D015415:Biomarkers; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D006147:Guanine; C078307:8-oxo-7,8-dihydrodeoxyguanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; C087259:3-chlorotyrosine