Human thioredoxin attenuates hypoxia-reoxygenation injury of murine endothelial cells in a thiol-free condition

Citation
N. Isowa et al., Human thioredoxin attenuates hypoxia-reoxygenation injury of murine endothelial cells in a thiol-free condition, J CELL PHYS, 182(1), 2000, pp. 33-40
Citations number
46
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELLULAR PHYSIOLOGY
ISSN journal
0021-9541 → ACNP
Volume
182
Issue
1
Year of publication
2000
Pages
33 - 40
Database
ISI
SICI code
0021-9541(200001)182:1<33:HTAHIO>2.0.ZU;2-F
Abstract
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 fro m ischemia-reperfusion induced injury. To elucidate mechanisms of the prote ctive effect, a hypoxia-reoxygenation (H-R) injury model was developed usin g 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 o f cells decreased significantly after 1 h of hypoxic incubation followed by 1 h of reoxygenation. The injury was reduced by ADF/hTRX (100 mu M) 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 condit ion, intracellular hydrogen peroxide production was increased, which was as sociated with a decrease in glutathione level. NAC (10 mM) attenuated these changes whereas ADF/hTRX (100 mu M) did not. These results suggest that al though both ADF/hTRX and NAC protected cells from H-R injury, the underlyin g mechanisms are different. Because the cytoprotective effect of ADF/hTRX o ccurs in the thiol-free condition, it must be mediated via a novel mechanis m other than enhancing thiol uptake. The additive cytoprotective effect bet ween ADF/hTRX and NAC suggests that we should combine these two agents clin ically. J. Cell. Physiol. 182:33-40, 2000. (C) 2000 Wiley-Liss, Inc.