Thioredoxin reduces post-ischemic myocardial apoptosis by reducing oxidative/nitrative stress.
Publication/Presentation Date
10-1-2006
Abstract
BACKGROUND AND PURPOSE: Thioredoxin (Trx) is an oxidoreductase that prevents free radical-induced cell death in cultured cells. Here we assessed the mechanism(s) underlying the cardioprotective effects of Trx in vivo.
EXPERIMENTAL APPROACH: The effects of myocardial ischemia (30 min) and reperfusion were measured in mice, with assays of myocardial apoptosis, superoxide production, NOx and nitrotyrosine content, and myocardial infarct size. Recombinant human Trx (rhTrx, 0.7-20 mg kg(-1), i.p.) was given 10 min before reperfusion.
KEY RESULTS: Treatment with 2 mg kg(-1) rhTrx significantly decreased myocardial apoptosis and reduced infarct size (P< 0.01). Nitrotyrosine content of cardiomyocytes was markedly reduced in rhTrx-treated animals (P< 0.01). To further identify the mechanisms by which rhTrx may exert its anti-nitrative effect, iNOS expression and production of NOx and superoxide were determined. Treatment with rhTrx had no significant effect on iNOS expression or NOx content in the ischemic/reperfused heart. However, it markedly upregulated mSOD and reduced tissue superoxide content. To further establish a causative link between the anti- peroxynitrite effect and the cardioprotective effect of rhTrx, cultured adult cardiomyocytes were incubated with SIN-1, a peroxynitrite donor, (50 microM for 3 h) resulting in a nitrotyrosine content comparable to that seen in the ischemic/reperfused heart and causing significant cardiomyocyte apoptosis (P< 0.01). Treatment with rhTrx markedly decreased SIN-1 induced apoptosis (P< 0.01).
CONCLUSIONS AND IMPLICATIONS: These results demonstrate that Trx is a novel anti-apoptotic and cardioprotective molecule that exerts its cardioprotective effects by reducing ischemia/reperfusion-induced oxidative/nitrative stress.
Volume
149
Issue
3
First Page
311
Last Page
318
ISSN
0007-1188
Published In/Presented At
Tao, L., Gao, E., Hu, A., Coletti, C., Wang, Y., Christopher, T. A., Lopez, B. L., Koch, W., & Ma, X. L. (2006). Thioredoxin reduces post-ischemic myocardial apoptosis by reducing oxidative/nitrative stress. British journal of pharmacology, 149(3), 311–318. https://doi.org/10.1038/sj.bjp.0706853
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
16921396
Department(s)
Administration and Leadership
Document Type
Article