Signaling Pathway for Endothelin-1- and Phenylephrine-Induced cAMP Response Element Binding Protein Activation in Rat Ventricular Myocytes: Role of Inositol 1,4,5-Trisphosphate Receptors and CaMKII
Background/Aims: Endothelin-1 (ET-1) and the α1-adrenoceptor agonist phenylephrine (PE) activate cAMP response element binding protein (CREB), a transcription factor implicated in cardiac hypertrophy. The signaling pathway involved in CREB activation by these hypertrophic stimuli is poorly understoo...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2017-01-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/456422 |
| _version_ | 1819132253219848192 |
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| author | Krishna P. Subedi Min-Jeong Son Bojjibabu Chidipi Seong-Woo Kim Jun Wang Kyeong-Hee Kim Sun-Hee Woo Joon-Chul Kim |
| author_facet | Krishna P. Subedi Min-Jeong Son Bojjibabu Chidipi Seong-Woo Kim Jun Wang Kyeong-Hee Kim Sun-Hee Woo Joon-Chul Kim |
| author_sort | Krishna P. Subedi |
| collection | DOAJ |
| description | Background/Aims: Endothelin-1 (ET-1) and the α1-adrenoceptor agonist phenylephrine (PE) activate cAMP response element binding protein (CREB), a transcription factor implicated in cardiac hypertrophy. The signaling pathway involved in CREB activation by these hypertrophic stimuli is poorly understood. We examined signaling pathways for ET-1- or PE-induced cardiac CREB activation. Methods: Western blotting was performed with pharmacological and genetic interventions in rat ventricular myocytes. Results: ET-1 and PE increased CREB phosphorylation, which was inhibited by blockade of phospholipase C, the extracellular-signal-regulated kinase 1/2 (ERK1/2) pathway, protein kinase C (PKC) or Ca2+-calmodulin-dependent protein kinase II (CaMKII). Intracellular Ca2+ buffering decreased ET-1- and PE-induced CREB phosphorylation by ≥80%. Sarcoplasmic reticulum Ca2+ pump inhibitor, inositol 1,4,5-trisphosphate receptor (IP3R) blockers, or type 2 IP3R (IP3R2) knock-out abolished ET-1- or PE-induced CREB phosphorylation. ET-1 and PE increased phosphorylation of CaMKII and ERK1/2, which was eliminated by IP3R blockade/knock-out or PKC inhibition. Activation of CaMKII, but not ERK1/2, by these agonists was sensitive to Ca2+ buffering or to Gö6976, the inhibitor of Ca2+-dependent PKC and protein kinase D (PKD). Conclusion: CREB phosphorylation by ET-1 and PE may be mainly mediated by IP3R2/Ca2+-PKC-PKD-CaMKII signaling with a minor contribution by ERK1/2, linked to IP3R2 and Ca2+-independent PKC, in ventricular myocytes. |
| first_indexed | 2024-12-22T09:28:28Z |
| format | Article |
| id | doaj.art-8efb949f655449b5a13e7f4c0eaaea92 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-22T09:28:28Z |
| publishDate | 2017-01-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-8efb949f655449b5a13e7f4c0eaaea922022-12-21T18:31:01ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-01-0141139941210.1159/000456422456422Signaling Pathway for Endothelin-1- and Phenylephrine-Induced cAMP Response Element Binding Protein Activation in Rat Ventricular Myocytes: Role of Inositol 1,4,5-Trisphosphate Receptors and CaMKIIKrishna P. SubediMin-Jeong SonBojjibabu ChidipiSeong-Woo KimJun WangKyeong-Hee KimSun-Hee WooJoon-Chul KimBackground/Aims: Endothelin-1 (ET-1) and the α1-adrenoceptor agonist phenylephrine (PE) activate cAMP response element binding protein (CREB), a transcription factor implicated in cardiac hypertrophy. The signaling pathway involved in CREB activation by these hypertrophic stimuli is poorly understood. We examined signaling pathways for ET-1- or PE-induced cardiac CREB activation. Methods: Western blotting was performed with pharmacological and genetic interventions in rat ventricular myocytes. Results: ET-1 and PE increased CREB phosphorylation, which was inhibited by blockade of phospholipase C, the extracellular-signal-regulated kinase 1/2 (ERK1/2) pathway, protein kinase C (PKC) or Ca2+-calmodulin-dependent protein kinase II (CaMKII). Intracellular Ca2+ buffering decreased ET-1- and PE-induced CREB phosphorylation by ≥80%. Sarcoplasmic reticulum Ca2+ pump inhibitor, inositol 1,4,5-trisphosphate receptor (IP3R) blockers, or type 2 IP3R (IP3R2) knock-out abolished ET-1- or PE-induced CREB phosphorylation. ET-1 and PE increased phosphorylation of CaMKII and ERK1/2, which was eliminated by IP3R blockade/knock-out or PKC inhibition. Activation of CaMKII, but not ERK1/2, by these agonists was sensitive to Ca2+ buffering or to Gö6976, the inhibitor of Ca2+-dependent PKC and protein kinase D (PKD). Conclusion: CREB phosphorylation by ET-1 and PE may be mainly mediated by IP3R2/Ca2+-PKC-PKD-CaMKII signaling with a minor contribution by ERK1/2, linked to IP3R2 and Ca2+-independent PKC, in ventricular myocytes.http://www.karger.com/Article/FullText/456422cAMP response element binding proteinInositol 1,4,5-trisphosphate receptorProtein kinase CCa2+-calmodulin-dependent protein kinase IIVentricular myocytes |
| spellingShingle | Krishna P. Subedi Min-Jeong Son Bojjibabu Chidipi Seong-Woo Kim Jun Wang Kyeong-Hee Kim Sun-Hee Woo Joon-Chul Kim Signaling Pathway for Endothelin-1- and Phenylephrine-Induced cAMP Response Element Binding Protein Activation in Rat Ventricular Myocytes: Role of Inositol 1,4,5-Trisphosphate Receptors and CaMKII Cellular Physiology and Biochemistry cAMP response element binding protein Inositol 1,4,5-trisphosphate receptor Protein kinase C Ca2+-calmodulin-dependent protein kinase II Ventricular myocytes |
| title | Signaling Pathway for Endothelin-1- and Phenylephrine-Induced cAMP Response Element Binding Protein Activation in Rat Ventricular Myocytes: Role of Inositol 1,4,5-Trisphosphate Receptors and CaMKII |
| title_full | Signaling Pathway for Endothelin-1- and Phenylephrine-Induced cAMP Response Element Binding Protein Activation in Rat Ventricular Myocytes: Role of Inositol 1,4,5-Trisphosphate Receptors and CaMKII |
| title_fullStr | Signaling Pathway for Endothelin-1- and Phenylephrine-Induced cAMP Response Element Binding Protein Activation in Rat Ventricular Myocytes: Role of Inositol 1,4,5-Trisphosphate Receptors and CaMKII |
| title_full_unstemmed | Signaling Pathway for Endothelin-1- and Phenylephrine-Induced cAMP Response Element Binding Protein Activation in Rat Ventricular Myocytes: Role of Inositol 1,4,5-Trisphosphate Receptors and CaMKII |
| title_short | Signaling Pathway for Endothelin-1- and Phenylephrine-Induced cAMP Response Element Binding Protein Activation in Rat Ventricular Myocytes: Role of Inositol 1,4,5-Trisphosphate Receptors and CaMKII |
| title_sort | signaling pathway for endothelin 1 and phenylephrine induced camp response element binding protein activation in rat ventricular myocytes role of inositol 1 4 5 trisphosphate receptors and camkii |
| topic | cAMP response element binding protein Inositol 1,4,5-trisphosphate receptor Protein kinase C Ca2+-calmodulin-dependent protein kinase II Ventricular myocytes |
| url | http://www.karger.com/Article/FullText/456422 |
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