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

doi:10.1016/S0960-0760(03)00006-2

Calreticulin inhibits the MEK1,2-ERK1,2 pathway in α₁-adrenergic receptor/G_h-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 journal › Article › peer-review

31 Citations (Scopus)

Abstract

In cardiac myocytes, stimulation of α₁-adrenoceptor (AR) leads to a hypertrophic phenotype. The G_h protein (transglutaminase II, TGII) is tissue type transglutaminase and transmits the α_1B-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 G_h 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 G_h on the activation of ERKs and inhibitory effects of CRT on α₁-adrenoceptor/G_h 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 G_h protein stimulated norepinephrine-induced ERKs activation, which was inhibited by α-adrenoceptor blocker (prazosin). Co-overexpression of G_h and CRT abolished norepinephrine-induced ERKs activation. Taken together, norepinephrine induces hypertrophy in neonatal rat cardiomyocytes through α₁-AR stimulation and G_h is partly involved in norepinephrine-induced MEK1,2/ERKs activation. Activation of G_h-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	https://doi.org/10.1016/S0960-0760(03)00006-2
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

UN SDGs

This output contributes to the following Sustainable Development Goal(s)

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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/G_h-stimulated hypertrophy of neonatal rat cardiomyocytes. In: Journal of Steroid Biochemistry and Molecular Biology. 2003 ; Vol. 84, No. 1. pp. 101-107.

@article{12c3cdd26d6d44dbb93e651c2489b57c,

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

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.",

author = "Lee, {Kyung Hye} and Namho Lee and Soyeon Lim and Heekyung Jung and Ko, {Young Guk} and Park, {Hyun Young} and Yangsoo Jang and Hakbae Lee and Hwang, {Ki Chul}",

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).",

year = "2003",

month = jan,

doi = "10.1016/S0960-0760(03)00006-2",

language = "English",

volume = "84",

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Calreticulin inhibits the MEK1,2-ERK1,2 pathway in α₁-adrenergic receptor/G_h-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 › peer-review

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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

N1 - 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).

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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