Glutathione-S-transferase A4-4 modulates oxidative stress in endothelium

Possible role in human atherosclerosis

Yongzhen Yang, Yusong Yang, Margaret B. Trent, Nonggao He, Scott D Lick, Piotr Zimniak, Yogesh C. Awasthi, Paul J. Boor

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

The role of α-class mammalian glutathione S-transferases (GSTs) in the protection of many cell types, including vascular smooth muscle cells, against oxidant damage has been demonstrated, but the role of GSTs in the endothelial cell is not well studied. In order to examine the role of GSTs in the endothelial cell, a stable transfection of mouse pancreatic islet endothelial cells (MS1) with cDNA of mGSTA4-4, mouse isozyme of GSTs with activity in vascular wall, was established. Transfected cells demonstrated significantly higher GSTs enzyme activity and expressed significantly increased resistance to the cytotoxicity of allylamine, acrolein, 4-hydroxy-2-nonenal (4-HNE), and H2O2 (P<0.05). A significantly higher rate of proliferation and lower baseline level of intracellular malondialdehyde (MDA) and 4-HNE were present when compared to wild-type or vector-transfected MS1 endothelial cells (P<0.05). Transfection protected MS1 endothelial cells from 4-HNE and H2O2 induced apoptosis by inhibiting phosphorylation of c-Jun N-terminal kinases (p-JNK) and consequent activation of p53 and Bax. In early human fibrous atherosclerotic plaques, immunohistochemical studies demonstrated marked induction of hGSTA4-4 in endothelial cells overlying plaque, and in proliferating plaque vascular smooth muscle cells. Our results indicate that endothelial cell mGSTA4-4 can play a key role in protecting blood vessels against oxidative stress and, thus, is likely to be a critical defense mechanism against oxidants that act as atherogens.

Original languageEnglish (US)
Pages (from-to)211-221
Number of pages11
JournalAtherosclerosis
Volume173
Issue number2
DOIs
StatePublished - Apr 2004
Externally publishedYes

Fingerprint

Glutathione Transferase
Endothelium
Atherosclerosis
Oxidative Stress
Endothelial Cells
Islets of Langerhans
Vascular Smooth Muscle
Oxidants
Smooth Muscle Myocytes
Transfection
Blood Vessels
Allylamine
Acrolein
Cytoprotection
JNK Mitogen-Activated Protein Kinases
Atherosclerotic Plaques
leukotriene-C4 synthase
Malondialdehyde
Isoenzymes
Complementary DNA

Keywords

  • 4-Hydroxy-2-nonenal
  • Atherosclerosis
  • Endothelium
  • Glutathione
  • Glutathione S-transferase
  • Lipid peroxidation
  • Oxidative stress

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Glutathione-S-transferase A4-4 modulates oxidative stress in endothelium : Possible role in human atherosclerosis. / Yang, Yongzhen; Yang, Yusong; Trent, Margaret B.; He, Nonggao; Lick, Scott D; Zimniak, Piotr; Awasthi, Yogesh C.; Boor, Paul J.

In: Atherosclerosis, Vol. 173, No. 2, 04.2004, p. 211-221.

Research output: Contribution to journalArticle

Yang, Yongzhen ; Yang, Yusong ; Trent, Margaret B. ; He, Nonggao ; Lick, Scott D ; Zimniak, Piotr ; Awasthi, Yogesh C. ; Boor, Paul J. / Glutathione-S-transferase A4-4 modulates oxidative stress in endothelium : Possible role in human atherosclerosis. In: Atherosclerosis. 2004 ; Vol. 173, No. 2. pp. 211-221.
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