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Dexmedetomidine-Induced Contraction in the Isolated Endothelium-Denuded Rat Aorta Involves PKC-δ-mediated JNK Phosphorylation

Vasoconstriction mediated by the highly selective alpha-2 adrenoceptor agonist dexmedetomidine leads to transiently increased blood pressure and severe hypertension. The dexmedetomidine-induced contraction involves the protein kinase C (PKC)-mediated pathway. However, the main PKC isoform involved i...

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Autores principales: Yu, Jongsun, Ok, Seong-Ho, Kim, Won Ho, Cho, Hyunhoo, Park, Jungchul, Shin, il-Woo, Lee, Heon Keun, Chung, Young-Kyun, Choi, Mun-Jeoung, Kwon, Seong-Chun, Sohn, Ju-Tae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571550/
https://www.ncbi.nlm.nih.gov/pubmed/26392810
http://dx.doi.org/10.7150/ijms.11952
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author Yu, Jongsun
Ok, Seong-Ho
Kim, Won Ho
Cho, Hyunhoo
Park, Jungchul
Shin, il-Woo
Lee, Heon Keun
Chung, Young-Kyun
Choi, Mun-Jeoung
Kwon, Seong-Chun
Sohn, Ju-Tae
author_facet Yu, Jongsun
Ok, Seong-Ho
Kim, Won Ho
Cho, Hyunhoo
Park, Jungchul
Shin, il-Woo
Lee, Heon Keun
Chung, Young-Kyun
Choi, Mun-Jeoung
Kwon, Seong-Chun
Sohn, Ju-Tae
author_sort Yu, Jongsun
collection PubMed
description Vasoconstriction mediated by the highly selective alpha-2 adrenoceptor agonist dexmedetomidine leads to transiently increased blood pressure and severe hypertension. The dexmedetomidine-induced contraction involves the protein kinase C (PKC)-mediated pathway. However, the main PKC isoform involved in the dexmedetomidine-induced contraction remains unknown. The goal of this in vitro study was to examine the specific PKC isoform that contributes to the dexmedetomidine-induced contraction in the isolated rat aorta. The endothelium-denuded rat aorta was suspended for isometric tension recording. Dexmedetomidine dose-response curves were generated in the presence or absence of the following inhibitors: the pan-PKC inhibitor, chelerythrine; the PKC-α and -β inhibitor, Go6976; the PKC-α inhibitor, safingol; the PKC-β inhibitor, ruboxistaurin; the PKC-δ inhibitor, rottlerin; the c-Jun NH(2)-terminal kinase (JNK) inhibitor, SP600125; and the myosin light chain kinase inhibitor, ML-7 hydrochloride. Western blot analysis was used to examine the effect of rottlerin on dexmedetomidine-induced PKC-δ expression and JNK phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) and to investigate the effect of dexmedetomidine on PKC-δ expression in VSMCs transfected with PKC-δ small interfering RNA (siRNA) or control siRNA. Chelerythrine as well as SP600125 and ML-7 hydrochloride attenuated the dexmedetomidine-induced contraction. Go6976, safingol, and ruboxistaurin had no effect on the dexmedetomidine-induced contraction, whereas rottlerin inhibited the dexmedetomidine-induced contraction. Dexmedetomidine induced PKC-δ expression, whereas rottlerin and PKC-δ siRNA transfection inhibited dexmedetomidine-induced PKC-δ expression. Dexmedetomidine also induced JNK phosphorylation, which was inhibited by rottlerin. Taken together, these results suggest that the dexmedetomidine-induced contraction involves PKC-δ-dependent JNK phosphorylation in the isolated rat aorta.
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spelling pubmed-45715502015-09-21 Dexmedetomidine-Induced Contraction in the Isolated Endothelium-Denuded Rat Aorta Involves PKC-δ-mediated JNK Phosphorylation Yu, Jongsun Ok, Seong-Ho Kim, Won Ho Cho, Hyunhoo Park, Jungchul Shin, il-Woo Lee, Heon Keun Chung, Young-Kyun Choi, Mun-Jeoung Kwon, Seong-Chun Sohn, Ju-Tae Int J Med Sci Research Paper Vasoconstriction mediated by the highly selective alpha-2 adrenoceptor agonist dexmedetomidine leads to transiently increased blood pressure and severe hypertension. The dexmedetomidine-induced contraction involves the protein kinase C (PKC)-mediated pathway. However, the main PKC isoform involved in the dexmedetomidine-induced contraction remains unknown. The goal of this in vitro study was to examine the specific PKC isoform that contributes to the dexmedetomidine-induced contraction in the isolated rat aorta. The endothelium-denuded rat aorta was suspended for isometric tension recording. Dexmedetomidine dose-response curves were generated in the presence or absence of the following inhibitors: the pan-PKC inhibitor, chelerythrine; the PKC-α and -β inhibitor, Go6976; the PKC-α inhibitor, safingol; the PKC-β inhibitor, ruboxistaurin; the PKC-δ inhibitor, rottlerin; the c-Jun NH(2)-terminal kinase (JNK) inhibitor, SP600125; and the myosin light chain kinase inhibitor, ML-7 hydrochloride. Western blot analysis was used to examine the effect of rottlerin on dexmedetomidine-induced PKC-δ expression and JNK phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) and to investigate the effect of dexmedetomidine on PKC-δ expression in VSMCs transfected with PKC-δ small interfering RNA (siRNA) or control siRNA. Chelerythrine as well as SP600125 and ML-7 hydrochloride attenuated the dexmedetomidine-induced contraction. Go6976, safingol, and ruboxistaurin had no effect on the dexmedetomidine-induced contraction, whereas rottlerin inhibited the dexmedetomidine-induced contraction. Dexmedetomidine induced PKC-δ expression, whereas rottlerin and PKC-δ siRNA transfection inhibited dexmedetomidine-induced PKC-δ expression. Dexmedetomidine also induced JNK phosphorylation, which was inhibited by rottlerin. Taken together, these results suggest that the dexmedetomidine-induced contraction involves PKC-δ-dependent JNK phosphorylation in the isolated rat aorta. Ivyspring International Publisher 2015-09-04 /pmc/articles/PMC4571550/ /pubmed/26392810 http://dx.doi.org/10.7150/ijms.11952 Text en © 2015 Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
spellingShingle Research Paper
Yu, Jongsun
Ok, Seong-Ho
Kim, Won Ho
Cho, Hyunhoo
Park, Jungchul
Shin, il-Woo
Lee, Heon Keun
Chung, Young-Kyun
Choi, Mun-Jeoung
Kwon, Seong-Chun
Sohn, Ju-Tae
Dexmedetomidine-Induced Contraction in the Isolated Endothelium-Denuded Rat Aorta Involves PKC-δ-mediated JNK Phosphorylation
title Dexmedetomidine-Induced Contraction in the Isolated Endothelium-Denuded Rat Aorta Involves PKC-δ-mediated JNK Phosphorylation
title_full Dexmedetomidine-Induced Contraction in the Isolated Endothelium-Denuded Rat Aorta Involves PKC-δ-mediated JNK Phosphorylation
title_fullStr Dexmedetomidine-Induced Contraction in the Isolated Endothelium-Denuded Rat Aorta Involves PKC-δ-mediated JNK Phosphorylation
title_full_unstemmed Dexmedetomidine-Induced Contraction in the Isolated Endothelium-Denuded Rat Aorta Involves PKC-δ-mediated JNK Phosphorylation
title_short Dexmedetomidine-Induced Contraction in the Isolated Endothelium-Denuded Rat Aorta Involves PKC-δ-mediated JNK Phosphorylation
title_sort dexmedetomidine-induced contraction in the isolated endothelium-denuded rat aorta involves pkc-δ-mediated jnk phosphorylation
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571550/
https://www.ncbi.nlm.nih.gov/pubmed/26392810
http://dx.doi.org/10.7150/ijms.11952
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