Abstract
In cardiac myocytes, stimulation of α1-adrenoceptor (AR) leads to a hypertrophic phenotype. The Gh protein (transglutaminase II, TGII) is tissue type transglutaminase and transmits the α1B-adrenoceptor signal with GTPase activity. Recently, it has been shown that the calreticulin (CRT) down-regulates both GTP binding and transglutaminase activities of TGII. To elucidate whether Gh mediates norepinephrine-stimulated intracellular signal transductions leading to activation of extracellular signal-regulated kinases (ERKs) and neonatal rat cardiomyocyte hypertrophy, we examined the effects of Gh on the activation of ERKs and inhibitory effects of CRT on α1-adrenoceptor/Gh signaling. In neonatal rat cardiomyocytes, norepinephrine-induced ERKs activation was inhibited by an α1-adrenoceptor blocker (prazosin), but not by an β-adrenoceptor blocker (propranolol). Overexpression of the Gh protein stimulated norepinephrine-induced ERKs activation, which was inhibited by α-adrenoceptor blocker (prazosin). Co-overexpression of Gh and CRT abolished norepinephrine-induced ERKs activation. Taken together, norepinephrine induces hypertrophy in neonatal rat cardiomyocytes through α1-AR stimulation and Gh is partly involved in norepinephrine-induced MEK1,2/ERKs activation. Activation of Gh-mediated MEK1,2/ERKs was completely inhibited by CRT.
Original language | English |
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Pages (from-to) | 101-107 |
Number of pages | 7 |
Journal | Journal of Steroid Biochemistry and Molecular Biology |
Volume | 84 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2003 Jan |
Bibliographical note
Funding Information:This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (HMP-00-GN-01-0001).
All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Endocrinology
- Clinical Biochemistry
- Cell Biology