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 |
|---|---|
| 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 |
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All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Endocrinology
- Clinical Biochemistry
- Cell Biology
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Calreticulin inhibits the MEK1,2-ERK1,2 pathway in α1-adrenergic receptor/Gh-stimulated hypertrophy of neonatal rat cardiomyocytes. / Lee, Kyung Hye; Lee, Namho; Lim, Soyeon; Jung, Heekyung; Ko, Young Guk; Park, Hyun Young; Jang, Yangsoo; Lee, Hakbae; Hwang, Ki Chul.
In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 84, No. 1, 01.2003, p. 101-107.Research output: Contribution to journal › Article
TY - JOUR
T1 - Calreticulin inhibits the MEK1,2-ERK1,2 pathway in α1-adrenergic receptor/Gh-stimulated hypertrophy of neonatal rat cardiomyocytes
AU - Lee, Kyung Hye
AU - Lee, Namho
AU - Lim, Soyeon
AU - Jung, Heekyung
AU - Ko, Young Guk
AU - Park, Hyun Young
AU - Jang, Yangsoo
AU - Lee, Hakbae
AU - Hwang, Ki Chul
PY - 2003/1
Y1 - 2003/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0344837797&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0344837797&partnerID=8YFLogxK
U2 - 10.1016/S0960-0760(03)00006-2
DO - 10.1016/S0960-0760(03)00006-2
M3 - Article
C2 - 12648529
AN - SCOPUS:0344837797
VL - 84
SP - 101
EP - 107
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
SN - 0960-0760
IS - 1
ER -