Ajaz Ahmad Waza1, Khurshid Andrabi1, Mahboob Ul Hussain2. 1. Department of Biotechnology, University of Kashmir, India. 2. Department of Biotechnology, University of Kashmir, India. Electronic address: mahboob@kashmiruniversity.ac.in.
Abstract
PURPOSE OF RESEARCH: We have recently shown that adenosine-triphosphate-sensitive potassium [K(+)(ATP)] channel protein subunit, Kir6.1 is a phosphospecific interaction partner of the gap-junction protein connexin43 (Cx43). Since, both Cx43 and K(+)(ATP) are known to be involved in cell survival during hypoxia, we addressed the question, whether the interaction between Cx43 and K(+)(ATP) has a role in protecting cell against hypoxia-induced cell death. PRINCIPLE RESULTS: We report here that the Kir6.1 protein interacts, in a phosphospecific manner with Cx43 in the mitochondria of cardiomyocytic cell line H9C2. The hypoxia for 12-h resulted in the appreciable increase in the phosphorylation at the serine 262 (S262) of the Cx43 with the concomitant increase in the Cx43 and Kir6.1 interaction. Moreover, the increased interaction was mediated by a signaling pathway involving PKC and more specifically by PKC epsilon. Functional implications of the association between the Cx43 and Kir6.1 were found to prevent mitochondria mediated hypoxia induced cell apoptosis. MAJOR CONCLUSIONS: Our results demonstrate that PKC epsilon regulates the interaction between Cx43 and Kir6.1 in the cardiomyocyte mitochondria and this interaction prevents hypoxia induced cell death. Our results provide an interesting lead in developing effective strategies to protect cardiomyocytes from hypoxia/ischemia induced cell death.
PURPOSE OF RESEARCH: We have recently shown that adenosine-triphosphate-sensitive potassium [K(+)(ATP)] channel protein subunit, Kir6.1 is a phosphospecific interaction partner of the gap-junction protein connexin43 (Cx43). Since, both Cx43 and K(+)(ATP) are known to be involved in cell survival during hypoxia, we addressed the question, whether the interaction between Cx43 and K(+)(ATP) has a role in protecting cell against hypoxia-induced cell death. PRINCIPLE RESULTS: We report here that the Kir6.1 protein interacts, in a phosphospecific manner with Cx43 in the mitochondria of cardiomyocytic cell line H9C2. The hypoxia for 12-h resulted in the appreciable increase in the phosphorylation at the serine 262 (S262) of the Cx43 with the concomitant increase in the Cx43 and Kir6.1 interaction. Moreover, the increased interaction was mediated by a signaling pathway involving PKC and more specifically by PKC epsilon. Functional implications of the association between the Cx43 and Kir6.1 were found to prevent mitochondria mediated hypoxia induced cell apoptosis. MAJOR CONCLUSIONS: Our results demonstrate that PKC epsilon regulates the interaction between Cx43 and Kir6.1 in the cardiomyocyte mitochondria and this interaction prevents hypoxia induced cell death. Our results provide an interesting lead in developing effective strategies to protect cardiomyocytes from hypoxia/ischemia induced cell death.
Authors: Antonio Rodríguez-Sinovas; Jose Antonio Sánchez; Laura Valls-Lacalle; Marta Consegal; Ignacio Ferreira-González Journal: Int J Mol Sci Date: 2021-04-23 Impact factor: 5.923
Authors: Luc Leybaert; Paul D Lampe; Stefan Dhein; Brenda R Kwak; Peter Ferdinandy; Eric C Beyer; Dale W Laird; Christian C Naus; Colin R Green; Rainer Schulz Journal: Pharmacol Rev Date: 2017-10 Impact factor: 25.468