Isoproterenol activates extracellular signal-regulated protein kinases in cardiomyocytes through calcineurin

Citation
Yz. Zou et al., Isoproterenol activates extracellular signal-regulated protein kinases in cardiomyocytes through calcineurin, CIRCULATION, 104(1), 2001, pp. 102-108
Citations number
38
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
CIRCULATION
ISSN journal
00097322 → ACNP
Volume
104
Issue
1
Year of publication
2001
Pages
102 - 108
Database
ISI
SICI code
0009-7322(20010703)104:1<102:IAESPK>2.0.ZU;2-#
Abstract
Background-Extracellular signal-regulated kinases (ERKs) and calcineurin ha ve been reported to play important roles in the development of cardiac hype rtrophy. We examined hen the relation between calcineurin and ERKs in cardi omyocytes. Methods and Results-Isoproterenol activated ERKs in cultured cardiomyocytes of neonatal rats, and the activation was abolished by chelation of extrace llular Ca2+ with EGTA, blockade of L-type Ca2+ channels with nifedipine, or depletion of intracellular Ca2+ stores with thapsigargin. Isoproterenol-in duced activation of ERKs was also significantly suppressed by calcineurin i nhibitors in cultured cardiomyocytes as well as in the hearts of mice. Isop roterenol failed to activate ERKs in either the cultured cardiomyocytes or the hearts of mice that overexpress the dominant negative mutant of calcine urin. Isoproterenol elevated intracellular Ca2+ levels at both systolic and diastolic phases and dose-dependently activated calcineurin. Inhibition of calcineurin also attenuated isoproterenol-stimulated phosphorylation of Sr c, She, and Raf-l kinase. The immunocytochemistry revealed that calcineurin was localized in the Z band, and isoproterenol induced translocation of ca lcineurin and ERKs into the nucleus. Conclusions-Calcineurin, which is activated by marked elevation of intracel lular Ca2+ levels by the Ca2+-induced Ca2+ release mechanism, regulates iso proterenol-induced activation of ERKs in cardiomyocytes.