Amino acid supplementation differentially modulates STAT1 and STAT3 activation in the myocardium exposed to ischemia/reperfusion injury

作者：Scarabelli Tiziano M; Townsend Paul A; Scarabelli Carol Chen; Yuan Zhaokan; McCauley Roy B; Di Rezze Justin; Patel David; Putt Jeff; Allebban Zuhair; Abboud John; Chilukuri Karuna; Gardin Julius; Saravolatz Louis; Knight Richard A; Latchman David S; Stephanou Anastasis^*

来源：American Journal of Cardiology, 2008, 101(11A): 63E-68E.

DOI：10.1016/j.amjcard.2008.03.003

We have previously demonstrated that the transcription factor STAT1 plays a critical role in promoting apoptotic cell death, whereas the related STAT3 family member may antagonize STAT1 and protect cardiac myocytes from ischemia/reperfusion (I/R) injury. More recently we demonstrated that long-term nutritional supplementation with mixed amino acids (AAs) can enhance myocyte survival by preserving mitochondrial functional capacity during I/R injury. We therefore investigated whether short-term nutritional supplementation with the same AA mixture has any effects on STAT1 or STAT3 activation in the Langendorff perfused rat heart exposed to I/R injury. In Sprague-Dawley rats given a single oral dose of a mixture of mainly essential L-AA (1 g/kg), and exposed, after 6 hours, to 35 minutes of ischemia, followed by 120 minutes of reperfusion, AA supplementation prolonged STAT3 activation/phosphorylation, while STAT1 activation was reduced. Enhanced STAT3 phosphorylation paralleled a reduction in expression of Fas, a known STAT1 target gene and proapoptotic marker that is upregulated after I/R. Moreover, abrogation of STAT3 activation by means of the JAK inhibitor AG490, reduced, but did not abolish, the cardioprotective effects of AA supplementation after I/R. These results show that modulation of the functional balance between STAT3 and STAT1, with preferential activation of prosurvival STAT3 over the proapoptotic STAT1, represents a mechanism by means of which short-term oral supplementation with mixed AAs protects the heart from I/R injury.

• 出版日期2008-6-2