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Human thioredoxin attenuates hypoxia‐reoxygenation injury of murine endothelial cells in a thiol‐free condition
Author(s) -
Isowa Noritaka,
Yoshimura Takashi,
Kosaka Shinji,
Liu Mingyao,
Hitomi Shigeki,
Yodoi Junji,
Wada Hiromi
Publication year - 2000
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(200001)182:1<33::aid-jcp4>3.0.co;2-5
Subject(s) - thiol , thioredoxin , glutathione , chemistry , intracellular , hypoxia (environmental) , microbiology and biotechnology , biochemistry , biology , oxidative stress , enzyme , oxygen , organic chemistry
The adult T cell leukemia‐derived factor (ADF), or human thioredoxin (hTRX), has a radical scavenging effect similar to that of N‐acetyl cysteine (NAC). We have recently shown that ADF/hTRX protects the lung and the heart from ischemia‐reperfusion induced injury. To elucidate mechanisms of the protective effect, a hypoxia‐reoxygenation (H‐R) injury model was developed using a murine endothelial cell line, cultured in a thiol‐free medium. In this condition, cells became much more vulnerable to H‐R injury. The viability of cells decreased significantly after 1 h of hypoxic incubation followed by 1 h of reoxygenation. The injury was reduced by ADF/hTRX (100 μM) or NAC (10 mM). These two agents also demonstrated an additive protective effect. When cells were cultured in thiol‐free medium for 2 h in a normoxic condition, intracellular hydrogen peroxide production was increased, which was associated with a decrease in glutathione level. NAC (10 mM) attenuated these changes whereas ADF/hTRX (100 μM) did not. These results suggest that although both ADF/hTRX and NAC protected cells from H‐R injury, the underlying mechanisms are different. Because the cytoprotective effect of ADF/hTRX occurs in the thiol‐free condition, it must be mediated via a novel mechanism other than enhancing thiol uptake. The additive cytoprotective effect between ADF/hTRX and NAC suggests that we should combine these two agents clinically. J. Cell. Physiol. 182:33–40, 2000. © 2000 Wiley‐Liss, Inc.