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Angiotensin-converting enzyme 2 catalytic activity in human plasma is masked by an endogenous inhibitor

Lew — 2008-04-29T05:11:11-00:00

Experimental Physiology, Vol. 93, No. 5. (May 2008), pp. 685-693.

Biochemical approaches for discovering proteinprotein interactions

Miernyk — 2008-02-08T00:50:26-00:00

The Plant Journal, Vol. 53, No. 4. (February 2008), pp. 597-609.

Specific inhibition of Stat3 signal transduction by PIAS3.

CD Chung — 2008-04-19T14:12:28-00:00

Science (New York, N.Y.), Vol. 278, No. 5344. (5 December 1997), pp. 1803-1805.

The signal transducer and activator of transcription-3 (Stat3) protein is activated by the interleukin 6 (IL-6) family of cytokines, epidermal growth factor, and leptin. A protein named PIAS3 (protein inhibitor of activated STAT) that binds to Stat3 was isolated and characterized. The association of PIAS3 with Stat3 in vivo was only observed in cells stimulated with ligands that cause the activation of Stat3. PIAS3 blocked the DNA-binding activity of Stat3 and inhibited Stat3-mediated gene activation. Although Stat1 is also phosphorylated in response to IL-6, PIAS3 did not interact with Stat1 or affect its DNA-binding or transcriptional activity. The results indicate that PIAS3 is a specific inhibitor of Stat3.

Protective effects of exercise and phosphoinositide 3-kinase(p110alpha) signaling in dilated and hypertrophic cardiomyopathy.

JR McMullen — 2008-04-15T15:00:24-00:00

Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 2. (9 January 2007), pp. 612-617.

Physical activity protects against cardiovascular disease, and physiological cardiac hypertrophy associated with regular exercise is usually beneficial, in marked contrast to pathological hypertrophy associated with disease. The p110alpha isoform of phosphoinositide 3-kinase (PI3K) plays a critical role in the induction of exercise-induced hypertrophy. Whether it or other genes activated in the athlete's heart might have an impact on cardiac function and survival in a setting of heart failure is unknown. To examine whether progressive exercise training and PI3K(p110alpha) activity affect survival and/or cardiac function in two models of heart disease, we subjected a transgenic mouse model of dilated cardiomyopathy (DCM) to swim training, genetically crossed cardiac-specific transgenic mice with increased or decreased PI3K(p110alpha) activity to the DCM model, and subjected PI3K(p110alpha) transgenics to acute pressure overload (ascending aortic constriction). Life-span, cardiac function, and molecular markers of pathological hypertrophy were examined. Exercise training and increased cardiac PI3K(p110alpha) activity prolonged survival in the DCM model by 15-20%. In contrast, reduced PI3K(p110alpha) activity drastically shortened lifespan by approximately 50%. Increased PI3K(p110alpha) activity had a favorable effect on cardiac function and fibrosis in the pressure-overload model and attenuated pathological growth. PI3K(p110alpha) signaling negatively regulated G protein-coupled receptor stimulated extracellular responsive kinase and Akt (via PI3K, p110gamma) activation in isolated cardiomyocytes. These findings suggest that exercise and enhanced PI3K(p110alpha) activity delay or prevent progression of heart disease, and that supraphysiologic activity can be beneficial. Identification of genes important for hypertrophy in the athlete's heart could offer new strategies for treating heart failure.