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International Journal Of Bilogical Sciences

.: Home > International Journal Of Bilogical Sciences > 2014 > Volume 10 Number 10 > Jiseok Baik1, Seong-Ho Ok2, Hyunhoo Cho3, Jongsun Yu3, Woochan Kim3, In-Koo Nam3, Mun-Jeoung Choi4, Heon-Keun Lee2, Ju-Tae Sohn2

Dexmedetomidine-induced Contraction Involves Phosphorylation of Caldesmon by JNK in Endotheliumdenuded Rat Aortas

Jiseok Baik1, Seong-Ho Ok2, Hyunhoo Cho3, Jongsun Yu3, Woochan Kim3, In-Koo Nam3, Mun-Jeoung Choi4, Heon-Keun Lee2, Ju-Tae Sohn2
1. Department of Anesthesiology and Pain Medicine, Pusan National University Hospital, Biomed Research Institute, Pusan National University School of Medicine, Busan, Republic of Korea 2. Department of Anesthesiology and Pain Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Jinju, Republic of Korea 3. Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju, Republic of Korea 4. Department of Oral and Maxillofacial Surgery, Gyeongsang National University Hospital, Jinju, Republic of Korea These authors contributed equally to this study as co-first authors. Corresponding author: Ju-Tae Sohn, Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju, Republic of Korea. Fax: +82-55-750-8142, Tel.: +82-55-750-8586, E-mail: jtsohn@nonage.gsnu.ac.kr
Abstract :

Caldesmon, an inhibitory actin binding protein, binds to actin and inhibits actin-myosin interactions, whereas caldesmon phosphorylation reverses the inhibitory effect of caldesmon on actin-myosin interactions, potentially leading to enhanced contraction. The goal of this study was to investigate the cellular signaling pathway responsible for caldesmon phosphorylation, which is involved in the regulation of the contraction induced by dexmedetomidine (DMT), an alpha-2 adrenoceptor agonist, in endothelium-denuded rat aortas. SP600125 (a c-Jun NH2-terminal kinase [JNK] inhibitor) dose-response curves were generated in aortas that were pre-contracted with DMT or phorbol 12,13-dibutyrate (PDBu), a protein kinase C (PKC) activator. Dose-response curves to the PKC inhibitor chelerythrine were generated in rat aortas pre-contracted with DMT. The effects of SP600125 and rauwolscine (an alpha-2 adrenoceptor inhibitor) on DMT-induced caldesmon phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) were investigated by western blot analysis. PDBu-induced caldesmon and DMT-induced PKC phosphorylation in rat aortic VSMCs was investigated by western blot analysis. The effects of GF109203X (a PKC inhibitor) on DMT- or PDBu-induced JNK phosphorylation in VSMCs were assessed. SP600125 resulted in the relaxation of aortas that were pre-contracted with DMT or PDBu, whereas rauwolscine attenuated DMT-induced contraction. Chelerythrine resulted in the vasodilation of aortas pre-contracted with DMT. SP600125 and rauwolscine inhibited DMT-induced caldesmon phosphorylation. Additionally, PDBu induced caldesmon phosphorylation, and GF109203X attenuated the JNK phosphorylation induced by DMT or PDBu. DMT induced PKC phosphorylation in rat aortic VSMCs. These results suggest that alpha-2 adrenoceptor-mediated, DMT-induced contraction involves caldesmon phosphorylation that is mediated by JNK phosphorylation by PKC.

Keywords :
dexmedetomidine, contraction, alpha-2 adrenoceptor, caldesmon, c-Jun NH2-terminal kinase, protein kinase C, rat aorta

Date Deposited : 15 Feb 2016 10:35

Last Modified : 15 Feb 2016 10:35

Official URL: http://www.ijbs.com/v10i10

Volume 10, Number 10, - 2014 , ISSN 1449-2288

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