[The role of interferon-gamma in prevention of hydrogen peroxide-induced oxidative injury to vascular endothelium].
OBJECTIVE
To observe the protective effects of interferon-gamma (IFN-gamma) on hydrogen peroxide (H(2)O(2))-induced oxidative injury to vascular endothelial cell (VEC), and to explore the role of 26S proteasome protection against IFN-gamma-induced endothelial oxidative injury.


METHODS
A H(2)O(2)-induced VEC oxidative injury to cell and isolated organ models were reproduced in the current study. The VEC oxidative damage in cellular level was evaluated by the contents of lactate dehydrogenase (LDH) and malondialdehyde (MDA) in culture medium, and the degree of oxidative injury of VEC in isolated organ level was evaluated by acetylcholine (Ach)-induced endothelium- dependent vascular relaxation.


RESULTS
H(2)O(2) triggered the oxidative injury in cultured VEC in a dose- and time-dependent manner, characterized by an increased contents of LDH and MDA in culture medium (P<0.05 or P<0.01). The Ach-induced endothelium- dependent vascular relaxation was decreased, and as shown by a decrease in 10(-5) mol/L Ach induced maximum reaction of relaxation of vasculature from (95.82+/-9.25)% to (12.61+/-2.96)% (P<0.01). The damage to VEC induced by H(2)O(2) was diminished significantly after incubation with IFN-gamma (20 microg/L) for 48 hours, characterized by a decreased production of LDH and MDA (both P<0.05) and restoration of endothelium- dependent vasodilation, and Ach-induced maximum reaction of vascular relaxation was increased to (72.68+/-18.82)% (P<0.01). 26S proteasome inhibitor lactacystin could partly antagonize the protective effects of IFN-gamma on H(2)O(2)-induced oxidative injury.


CONCLUSIONS
IFN-gamma possesses protective effects on H(2)O(2)-induced oxidative injury to vascular endothelium, and its mechanism is at least partly related with 26S proteasome.
Zhou
Rong
R
the Second Department of Military Surgery Research Institute, the Third Military Medical University, Dapin g Hospital, Chongqing, China. zhourong200012@153.com
Liu
Liang-ming
LM
Hu
De-yao
DY
Cheng
Feng
F
Li
Qiang
Q
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation
D008315:Malondialdehyde; D007371:Interferon-gamma; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D000109:Acetylcholine