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- Title
Expression of active protein phosphatase 1 inhibitor-1 attenuates chronic beta-agonist-induced cardiac apoptosis.
- Authors
Guoli Chen; Xiaoyang Zhou; Florea, Stela; Jiang Qian; Wenfeng Cai; Zhiguo Zhang; Guo-Chang Fan; Lorenz, John; Hajjar, Roger J.; Kranias, Evangelia G.
- Abstract
Cardiac apoptosis has been considered an important contributing factor to heart failure. Several subcellular mechanisms, including increased protein phosphatase 1 activity, have been suggested to induce apoptosis. Protein phosphatase 1 is regulated by an endogenous inhibitor-1 (I-1) that is activated upon phosphorylation at threonine 35 via protein kinase A. Here, we tested whether cardiac-specific overexpression of a constitutively active (T35D, AA 1-65) inhibitor-1 (I-1c), could also affect cardiac apoptosis and heart failure progression induced by prolonged β-adrenergic stimulation. We found that either acute or chronic expression of I-1c reduced isoproterenol (ISO)-induced apoptosis assessed by nuclear condensation, TUNEL staining and DNA fragmentation. The beneficial effects of I-1c were associated with increased expression of the anti-apoptotic protein Bcl-2, decreased expression of the pro-apoptotic protein Bax and reduced levels of active caspases as well as increased activation of ERK. These findings suggest that mitochondrial signaling and ERK activation may be involved in the I-1c cardioprotective effects against apoptosis induced by prolonged β-adrenergic stimulation.
- Subjects
APOPTOSIS; CELL death; HEART diseases; CARDIAC arrest; CARDIOVASCULAR agents; PROTEIN kinases
- Publication
Basic Research in Cardiology, 2010, Vol 105, Issue 5, p573
- ISSN
0300-8428
- Publication type
Article
- DOI
10.1007/s00395-010-0106-3