Reduced expression of GSTM2 and increased oxidative stress in spontaneously hypertensive rat.
Human essential hypertension is a complex polygenic trait with underlying genetic components that remain unknown. The spontaneously hypertensive rat (SHR) is a well-characterized experimental model for essential hypertension. By comparative proteomics, we previously identified glutathione S-transferase, mu 2 (GSTM2), a protein involved in detoxification of reactive oxygen species, which had a significant reduction in left ventricles of 16-week-old SHR compared with WKY rats. In parallel, Western blotting and RT-PCR showed a similar reduction of GSTM2 in left ventricles and aortas of 4-, 8-, and 16-week-old SHR, which is before the onset of hypertension. This suggests that differential expression is not attributable to long-term changes in blood pressure. Meanwhile, the activities of GSTM2 were significantly decreased in different ages old SHR. Conversely, there was an enhanced generation of superoxide anion and activation of NADPH oxidase in SHR, which was accompanied by an increase in the protein expression of p47phox, a subunit of NADPH oxidase. These data suggest that it maybe a reduction in antioxidant defenses, evident by a reduced expression and activity of GSTM2, in the left ventricles and aortas of SHR that leads to increased levels of superoxide anion and activation of NADPH oxidase.
Zhou
Si-Gui
SG
Pharmacology and Toxicology Laboratory, School of Pharmaceutical Sciences, Sun Yat-sen University, 74 Zhongshan II Road, GuangZhou 510080, PR China.
Wang
Ping
P
Pi
Rong-Biao
RB
Gao
Jie
J
Fu
Jia-Jia
JJ
Fang
Jian
J
Qin
Jia
J
Zhang
Hui-Jie
HJ
Li
Rui-Fang
RF
Chen
Shao-Rui
SR
Tang
Fu-Tian
FT
Liu
Pei-Qing
PQ
D000375:Aging; D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000503:physiopathology; D001794:Blood Pressure; D004452:Echocardiography; D015971:Gene Expression Regulation, Enzymologic; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D006352:Heart Ventricles / Q000201:enzymology / Q000503:physiopathology; D006984:Hypertrophy; D015151:Immunoblotting; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D021122:Protein Subunits / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D013481:Superoxides / Q000378:metabolism; D013599:Systole
D021122:Protein Subunits; D012333:RNA, Messenger; D013481:Superoxides; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D005982:Glutathione Transferase; C412602:glutathione S-transferase Mu 2