Sphingosine-1-phosphate and endothelin-1 induce the expression of rgs16 protein in cardiac myocytes by transcriptional activation of the rgs16 gene
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Sphingosine-1-phosphate and endothelin-1 induce the expression of rgs16 protein in cardiac myocytes by transcriptional activation of the rgs16 gene. / Stuebe, Sabine; Wieland, Thomas; Kraemer, Elisabeth; Stritzky, Alexandra v; Schroeder, Diana; Seekamp, Sünje; Vogt, Andreas; Chen, Ching-Kang; Patten, Monica.
in: N-S ARCH PHARMACOL, Jahrgang 376, Nr. 5, 01.2008, S. 363-373.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Sphingosine-1-phosphate and endothelin-1 induce the expression of rgs16 protein in cardiac myocytes by transcriptional activation of the rgs16 gene
AU - Stuebe, Sabine
AU - Wieland, Thomas
AU - Kraemer, Elisabeth
AU - Stritzky, Alexandra v
AU - Schroeder, Diana
AU - Seekamp, Sünje
AU - Vogt, Andreas
AU - Chen, Ching-Kang
AU - Patten, Monica
PY - 2008/1
Y1 - 2008/1
N2 - The expression of the negative Regulator of G protein signaling 16 (RGS16) is rapidly induced in cardiomyocytes by various stimuli. To identify the promoter of the mouse RGS16 gene, a 1.8-kb deoxyribonucleic acid fragment 5' of the RGS16-coding region was subcloned into a firefly-luciferase reporter vector and four overlapping fragments were analyzed. The luciferase production was quantified in neonatal rat cardiac myocytes (NRCM). A 0.6-kb fragment that induced a tenfold increase in luciferase activity contained the minimal promoter sequence. Its activity was twofold stimulated by fetal calf serum, endothelin-1 (ET-1), and sphingosine 1-phosphate (S1P), which stimuli also elevated the level of RGS16 protein. Stimulation of NRCM with ET-1 induced activation of the monomeric GTPases RhoA and Rac1, whereas S1P and the selective S1P1 receptor agonist SEW2871 only induced a pronounced activation of Rac1. In accordance, the treatment with the Rho-, Rac-, and Cdc42-inactivating Clostridium difficile Toxin B (TcdB) 10463 inhibited ET-1 and S1P-induced transcriptional activation. The ET-1-induced activation was insensitive to pertussis toxin but selectively suppressed by the RhoA-C-specific C2I-C3 ADP-ribosyl transferase and the ET(B) receptor antagonist BQ788. The S1P-induced activation was specifically inhibited by pertussis toxin and the Rac-inactivating TcdB 1470. All stimulated transcriptional activity was abolished by the negative transcription factor Yin Yang 1 (YY1), which binds to a consensus sequence within the minimal promoter. Taken together, our data show that most likely ET(B)- and S1P1-receptors induce RGS16 protein expression in cardiac myocytes by increasing the transcriptional activity of the rgs16 gene. This activation is mediated by heterotrimeric G proteins, Rho GTPases, and is under negative control of the transcription factor YY1.
AB - The expression of the negative Regulator of G protein signaling 16 (RGS16) is rapidly induced in cardiomyocytes by various stimuli. To identify the promoter of the mouse RGS16 gene, a 1.8-kb deoxyribonucleic acid fragment 5' of the RGS16-coding region was subcloned into a firefly-luciferase reporter vector and four overlapping fragments were analyzed. The luciferase production was quantified in neonatal rat cardiac myocytes (NRCM). A 0.6-kb fragment that induced a tenfold increase in luciferase activity contained the minimal promoter sequence. Its activity was twofold stimulated by fetal calf serum, endothelin-1 (ET-1), and sphingosine 1-phosphate (S1P), which stimuli also elevated the level of RGS16 protein. Stimulation of NRCM with ET-1 induced activation of the monomeric GTPases RhoA and Rac1, whereas S1P and the selective S1P1 receptor agonist SEW2871 only induced a pronounced activation of Rac1. In accordance, the treatment with the Rho-, Rac-, and Cdc42-inactivating Clostridium difficile Toxin B (TcdB) 10463 inhibited ET-1 and S1P-induced transcriptional activation. The ET-1-induced activation was insensitive to pertussis toxin but selectively suppressed by the RhoA-C-specific C2I-C3 ADP-ribosyl transferase and the ET(B) receptor antagonist BQ788. The S1P-induced activation was specifically inhibited by pertussis toxin and the Rac-inactivating TcdB 1470. All stimulated transcriptional activity was abolished by the negative transcription factor Yin Yang 1 (YY1), which binds to a consensus sequence within the minimal promoter. Taken together, our data show that most likely ET(B)- and S1P1-receptors induce RGS16 protein expression in cardiac myocytes by increasing the transcriptional activity of the rgs16 gene. This activation is mediated by heterotrimeric G proteins, Rho GTPases, and is under negative control of the transcription factor YY1.
KW - Animals
KW - Animals, Newborn
KW - Bacterial Proteins/pharmacology
KW - Bacterial Toxins/pharmacology
KW - Cattle
KW - Cells, Cultured
KW - Endothelin-1/physiology
KW - Fetal Blood/metabolism
KW - Gene Expression Regulation
KW - Luciferases/metabolism
KW - Lysophospholipids/physiology
KW - Mice
KW - Myocytes, Cardiac
KW - Pertussis Toxin/pharmacology
KW - Promoter Regions, Genetic
KW - RGS Proteins/metabolism
KW - Rats
KW - Sphingosine/analogs & derivatives
KW - Transcription, Genetic
KW - YY1 Transcription Factor/metabolism
KW - rac1 GTP-Binding Protein/metabolism
KW - rhoA GTP-Binding Protein/metabolism
U2 - 10.1007/s00210-007-0214-2
DO - 10.1007/s00210-007-0214-2
M3 - SCORING: Journal article
C2 - 18046543
VL - 376
SP - 363
EP - 373
JO - N-S ARCH PHARMACOL
JF - N-S ARCH PHARMACOL
SN - 0028-1298
IS - 5
ER -