Calreticulin inhibits the MEK1,2-ERK1,2 pathway in α1-adrenergic receptor/Gh-stimulated hypertrophy of neonatal rat cardiomyocytes

Kyung Hye Lee, Namho Lee, Soyeon Lim, Heekyung Jung, Young Guk Ko, Hyun Young Park, Yangsoo Jang, Hakbae Lee, Ki Chul Hwang

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 languageEnglish
Pages (from-to)101-107
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume84
Issue number1
DOIs
Publication statusPublished - 2003 Jan

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Calreticulin
MAP Kinase Signaling System
Cardiac Myocytes
Adrenergic Receptors
Hypertrophy
Rats
Extracellular Signal-Regulated MAP Kinases
Chemical activation
Norepinephrine
Prazosin
Mitogen-Activated Protein Kinase 1
Signal transduction
Transglutaminases
GTP Phosphohydrolases
Guanosine Triphosphate
Propranolol
Signal Transduction
Proteins
Down-Regulation
Phenotype

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Lee, Kyung Hye ; Lee, Namho ; Lim, Soyeon ; Jung, Heekyung ; Ko, Young Guk ; Park, Hyun Young ; Jang, Yangsoo ; Lee, Hakbae ; Hwang, Ki Chul. / Calreticulin inhibits the MEK1,2-ERK1,2 pathway in α1-adrenergic receptor/Gh-stimulated hypertrophy of neonatal rat cardiomyocytes. In: Journal of Steroid Biochemistry and Molecular Biology. 2003 ; Vol. 84, No. 1. pp. 101-107.
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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.",
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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 journalArticle

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.

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