The signal transducer and activator of transcription (STAT) family are latent transcription factors involved in a variety of signal transduction pathways, including cell death cascades. STAT1 has been shown to have a crucial role in regulating cardiac cell apoptosis in the myocardium exposed to ischemia/reperfusion (I/R) injury. The free radical scavenger, tempol, is known to have cardioprotective properties, although little is known about the molecular mechanism(s) by which it acts. In the present study, we assessed the levels of phosphorylated STAT1 and STAT3 and examined whether tempol was able to affect STAT activation after in vivo cardiac I/R injury. We observed a reperfusion time-dependent increase in the tyrosine phosphorylation of STAT1 and STAT3 at residues 701 and 705, respectively. Here we show for the first time that tempol dramatically reduced STAT1 and 3 phosphorylation. The reduction in STAT1 and 3 phosphorylation was accompanied by a concomitant decrease in cellular malondialdehyde (MDA) levels. To verify the role of STAT1 in modulating the cardioprotective effect of tempol, rats were injected with the STAT1 activator, IFN-γ, and tempol during I/R injury. We found that the presence of IFN-γ abrogated the protective effects of tempol, suggesting that the protective effects of tempol may partly operate by decreasing the phosphorylation of STAT1. This study demonstrates that careful dissection of the molecular mechanisms that underpin I/R injury may reveal cardioprotective targets for future therapy.—McCormick, J,. Barry, S. P., Sivarajah, A., Stefanutti, G., Townsend, P. A., Lawrence, K. M., Eaton, S., Knight, R. A., Thiemermann, C., Latchman, D. S., Stephanou, A. Free radical scavenging inhibits stat phosphorylation following in vivo ischemia/reperfusion injury.
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Free radical scavenging inhibits STAT phosphorylation following in vivo ischemia/reperfusion injury
McCormick, James; Barry, Sean P.; Sivarajah, Ahila; Stefanutti, Giorgio; Townsend, Paul A.; Lawrence, Kevin M.; Eaton, Simon; Knight, Richard A.; Thiemermann, Christoph; Latchman, David S.; Stephanou, Anastasis
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, Volume 20 (12): 2115
Fed of American Socs for Experimental Biology – Oct 1, 2006
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