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Endotoxin induces desensitization of cardiac endothelin-1 receptor signaling by increased expression of RGS4 and RGS16

Standard

Endotoxin induces desensitization of cardiac endothelin-1 receptor signaling by increased expression of RGS4 and RGS16. / Patten, Monica; Bünemann, Jan; Thoma, Bryan; Krämer, Elisabeth; Thoenes, Martin; Stübe, Sabine; Mittmann, Clemens; Wieland, Thomas.

In: CARDIOVASC RES, Vol. 53, No. 1, 01.2002, p. 156-164.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Patten, M, Bünemann, J, Thoma, B, Krämer, E, Thoenes, M, Stübe, S, Mittmann, C & Wieland, T 2002, 'Endotoxin induces desensitization of cardiac endothelin-1 receptor signaling by increased expression of RGS4 and RGS16', CARDIOVASC RES, vol. 53, no. 1, pp. 156-164. https://doi.org/10.1016/s0008-6363(01)00443-6

APA

Patten, M., Bünemann, J., Thoma, B., Krämer, E., Thoenes, M., Stübe, S., Mittmann, C., & Wieland, T. (2002). Endotoxin induces desensitization of cardiac endothelin-1 receptor signaling by increased expression of RGS4 and RGS16. CARDIOVASC RES, 53(1), 156-164. https://doi.org/10.1016/s0008-6363(01)00443-6

Vancouver

Patten M, Bünemann J, Thoma B, Krämer E, Thoenes M, Stübe S et al. Endotoxin induces desensitization of cardiac endothelin-1 receptor signaling by increased expression of RGS4 and RGS16. CARDIOVASC RES. 2002 Jan;53(1):156-164. https://doi.org/10.1016/s0008-6363(01)00443-6

Bibtex

@article{117b17bdabf043eabc5b3dcf88240ea9,
title = "Endotoxin induces desensitization of cardiac endothelin-1 receptor signaling by increased expression of RGS4 and RGS16",
abstract = "OBJECTIVE: Endotoxin (LPS)-induced acute cardiac failure during sepsis is associated with alterations in G protein mediated signal transduction. We therefore examined the expression of the G proteins G(i), G(q), and G(s) and of four 'regulators of G protein signaling' (RGS) proteins, RGS1, RGS4, RGS5, and RGS16 in rat hearts.METHODS: For in vivo experiments, Wistar rats were treated with 600 microg/day E. coli LPS, intravenously) and hearts were excised after 6, 24 and 72 h. Cultured neonatal rat cardiomyocytes were treated with 4 microg/ml LPS for 24 and 72 h. Isolated membrane proteins were used for Western blot analysis and for evaluation of phospholipase C (PLC) activity. RGS16 mRNA was detected by RNAse protection.RESULTS: LPS induced G(i) protein 1.4-fold 72 h after in vivo administration of LPS, whereas expression of G(s) and G(q) was unaltered. After 6 h of LPS treatment, RGS16 mRNA was transiently up-regulated 3.7-fold, followed by transient protein induction (24 h: 2.5-fold; 72 h: 1.5-fold). Similarly, RGS4 protein was transiently induced (24 h: 3.1-fold; 72 h: 1.5-fold), whereas expression of RGS1 and RGS5 was not altered. Similar to the LPS-treated rat hearts, RGS16 expression was transiently induced by LPS in cultured neonatal rat cardiomyocytes (24 h: 1.6-fold, 72 h: 0.9-fold). To determine the functional consequences of the RGS protein induction phospholipase C (PLC) activity was analyzed in membranes obtained from solvent and LPS-treated hearts. Basal and endothelin-1-stimulated PLC activity was transiently repressed by LPS with a maximum after 24 h although no apparent changes in PLCbeta1 or endothelin receptor expression could be detected.CONCLUSION: These data suggest that the rapid up-regulation of cardiac RGS4 and RGS16 is associated with a desensitization of endothelin-1 receptor signaling. Up-regulation of these RGS proteins may thus be involved in the early onset of cardiac failure during sepsis.",
keywords = "Animals, Blotting, Western, Cells, Cultured, GTP-Binding Proteins/metabolism, Heart Failure/metabolism, Lipopolysaccharides/pharmacology, Male, Myocardium/metabolism, Proteins/genetics, RGS Proteins/genetics, RNA, Messenger/analysis, Rats, Rats, Wistar, Receptors, Endothelin/metabolism, Signal Transduction/drug effects, Type C Phospholipases/analysis",
author = "Monica Patten and Jan B{\"u}nemann and Bryan Thoma and Elisabeth Kr{\"a}mer and Martin Thoenes and Sabine St{\"u}be and Clemens Mittmann and Thomas Wieland",
year = "2002",
month = jan,
doi = "10.1016/s0008-6363(01)00443-6",
language = "English",
volume = "53",
pages = "156--164",
journal = "CARDIOVASC RES",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "1",

}

RIS

TY - JOUR

T1 - Endotoxin induces desensitization of cardiac endothelin-1 receptor signaling by increased expression of RGS4 and RGS16

AU - Patten, Monica

AU - Bünemann, Jan

AU - Thoma, Bryan

AU - Krämer, Elisabeth

AU - Thoenes, Martin

AU - Stübe, Sabine

AU - Mittmann, Clemens

AU - Wieland, Thomas

PY - 2002/1

Y1 - 2002/1

N2 - OBJECTIVE: Endotoxin (LPS)-induced acute cardiac failure during sepsis is associated with alterations in G protein mediated signal transduction. We therefore examined the expression of the G proteins G(i), G(q), and G(s) and of four 'regulators of G protein signaling' (RGS) proteins, RGS1, RGS4, RGS5, and RGS16 in rat hearts.METHODS: For in vivo experiments, Wistar rats were treated with 600 microg/day E. coli LPS, intravenously) and hearts were excised after 6, 24 and 72 h. Cultured neonatal rat cardiomyocytes were treated with 4 microg/ml LPS for 24 and 72 h. Isolated membrane proteins were used for Western blot analysis and for evaluation of phospholipase C (PLC) activity. RGS16 mRNA was detected by RNAse protection.RESULTS: LPS induced G(i) protein 1.4-fold 72 h after in vivo administration of LPS, whereas expression of G(s) and G(q) was unaltered. After 6 h of LPS treatment, RGS16 mRNA was transiently up-regulated 3.7-fold, followed by transient protein induction (24 h: 2.5-fold; 72 h: 1.5-fold). Similarly, RGS4 protein was transiently induced (24 h: 3.1-fold; 72 h: 1.5-fold), whereas expression of RGS1 and RGS5 was not altered. Similar to the LPS-treated rat hearts, RGS16 expression was transiently induced by LPS in cultured neonatal rat cardiomyocytes (24 h: 1.6-fold, 72 h: 0.9-fold). To determine the functional consequences of the RGS protein induction phospholipase C (PLC) activity was analyzed in membranes obtained from solvent and LPS-treated hearts. Basal and endothelin-1-stimulated PLC activity was transiently repressed by LPS with a maximum after 24 h although no apparent changes in PLCbeta1 or endothelin receptor expression could be detected.CONCLUSION: These data suggest that the rapid up-regulation of cardiac RGS4 and RGS16 is associated with a desensitization of endothelin-1 receptor signaling. Up-regulation of these RGS proteins may thus be involved in the early onset of cardiac failure during sepsis.

AB - OBJECTIVE: Endotoxin (LPS)-induced acute cardiac failure during sepsis is associated with alterations in G protein mediated signal transduction. We therefore examined the expression of the G proteins G(i), G(q), and G(s) and of four 'regulators of G protein signaling' (RGS) proteins, RGS1, RGS4, RGS5, and RGS16 in rat hearts.METHODS: For in vivo experiments, Wistar rats were treated with 600 microg/day E. coli LPS, intravenously) and hearts were excised after 6, 24 and 72 h. Cultured neonatal rat cardiomyocytes were treated with 4 microg/ml LPS for 24 and 72 h. Isolated membrane proteins were used for Western blot analysis and for evaluation of phospholipase C (PLC) activity. RGS16 mRNA was detected by RNAse protection.RESULTS: LPS induced G(i) protein 1.4-fold 72 h after in vivo administration of LPS, whereas expression of G(s) and G(q) was unaltered. After 6 h of LPS treatment, RGS16 mRNA was transiently up-regulated 3.7-fold, followed by transient protein induction (24 h: 2.5-fold; 72 h: 1.5-fold). Similarly, RGS4 protein was transiently induced (24 h: 3.1-fold; 72 h: 1.5-fold), whereas expression of RGS1 and RGS5 was not altered. Similar to the LPS-treated rat hearts, RGS16 expression was transiently induced by LPS in cultured neonatal rat cardiomyocytes (24 h: 1.6-fold, 72 h: 0.9-fold). To determine the functional consequences of the RGS protein induction phospholipase C (PLC) activity was analyzed in membranes obtained from solvent and LPS-treated hearts. Basal and endothelin-1-stimulated PLC activity was transiently repressed by LPS with a maximum after 24 h although no apparent changes in PLCbeta1 or endothelin receptor expression could be detected.CONCLUSION: These data suggest that the rapid up-regulation of cardiac RGS4 and RGS16 is associated with a desensitization of endothelin-1 receptor signaling. Up-regulation of these RGS proteins may thus be involved in the early onset of cardiac failure during sepsis.

KW - Animals

KW - Blotting, Western

KW - Cells, Cultured

KW - GTP-Binding Proteins/metabolism

KW - Heart Failure/metabolism

KW - Lipopolysaccharides/pharmacology

KW - Male

KW - Myocardium/metabolism

KW - Proteins/genetics

KW - RGS Proteins/genetics

KW - RNA, Messenger/analysis

KW - Rats

KW - Rats, Wistar

KW - Receptors, Endothelin/metabolism

KW - Signal Transduction/drug effects

KW - Type C Phospholipases/analysis

U2 - 10.1016/s0008-6363(01)00443-6

DO - 10.1016/s0008-6363(01)00443-6

M3 - SCORING: Journal article

C2 - 11744024

VL - 53

SP - 156

EP - 164

JO - CARDIOVASC RES

JF - CARDIOVASC RES

SN - 0008-6363

IS - 1

ER -