Expression of active protein phosphatase 1 inhibitor-1 attenuates chronic beta-agonist-induced cardiac apoptosis

Guoli Chen, Xiaoyang Zhou, Stela Florea, Jiang Qian, Wenfeng Cai, Zhiguo Zhang, Guo Chang Fan, John Lorenz, Roger J. Hajjar, Evangelia G. Kranias

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)573-581
Number of pages9
JournalBasic Research in Cardiology
Issue number5
StatePublished - Sep 2010

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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