Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiomyopathy presents a major health issue and is a leading cause of heart failure. Although a subset of familial cardiomyopathy is associated with genetic mutations, over 50% of cardiomyopathy is defined as idiopathic, the mechanisms underlying which are under intensive investigation. SUMO conjugation is a dynamic posttranslational modification that can be readily reversed by the activity of sentrin-specific proteases (SENPs). However, whether SENPs are implicated in heart disease pathophysiology remains unexplored. We observed a significant increase in the level of SENP5, a SUMO isopeptidase, in human idiopathic failing hearts. To reveal whether it plays a role in the pathogenesis of cardiac muscle disorders, we used a gain-of-function approach to overexpress SENP5 in murine cardiomyocytes (SENP5 transgenic, SENP5-Tg). Overexpression of SENP5 led to cardiac dysfunction, accompanied by decreased cardiomyocyte proliferation and elevated apoptosis. The increase in apoptosis preceded other detectable pathological changes, suggesting its causal link to cardiomyopathy. Further examination of SENP5-Tg hearts unveiled a decrease in SUMO attachment to dynamin related protein (Drp1), a factor critical for mitochondrial fission. Correspondingly, the mitochondria of SENP5-Tg hearts at an early developmental stage were significantly larger compared with those in the control hearts, suggesting that desumoylation of Drp1 at least partially accounts for the cardiac phenotypes observed in the SENP5-Tg mice. Finally, overexpression of Bcl2 in SENP5-Tg hearts improved cardiac function of SENP5-Tg mice, further supporting the notion that SENP5 mainly targets mitochondrial function in vivo. Our findings demonstrate an important role of the desumoylation enzyme SENP5 in the development of cardiac muscle disorders, and point to the SUMO conjugation pathway as a potential target in the prevention/treatment of cardiomyopathy. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease".
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PMID:SENP5, a SUMO isopeptidase, induces apoptosis and cardiomyopathy. 2512 87

SUMOylation regulates diverse cellular processes including transcription, cell cycle, protein stability, and apoptosis. A recent research has now revealed the role of SUMO1 in cardiac disorders. Studies have evidenced that failing heart induces SUMO2/3 conjugation. Moreover, increased SUMO2/3- dependent modification has been observed to result in congestive heart disease such as cardiac hypertrophy by promoting cardiac cell death. Also, few recent studies have confirmed the role of SUMOylation in cardiac protein degradation. On the other hand, over-expression of SENP5, SUMO2/3-specific deconjugation enzyme has been observed to result in dilated cardiomyopathy or cardiac failure. So, the present review article would enlighten the latest updates about SUMOylation and associated factors during cardiac disorders.
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PMID:SUMOylation in cardiac disorders - a review. 2842 47