title: Protein kinase C (PKC) mediated interaction between conexin43 (Cx43) and K(+)(ATP) channel subunit (Kir6.1) in cardiomyocyte mitochondria: Implications in cytoprotection against hypoxia induced cell apoptosis.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  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.affiliation: Department of Biotechnology, University of Kashmir, India.
authors.forename: Ajaz Ahmad
authors.initials: AA
authors.lastname: Waza
authors.affiliation: Department of Biotechnology, University of Kashmir, India.
authors.forename: Khurshid
authors.initials: K
authors.lastname: Andrabi
authors.affiliation: Department of Biotechnology, University of Kashmir, India. Electronic address: mahboob@kashmiruniversity.ac.in.
authors.forename: Mahboob Ul
authors.initials: MU
authors.lastname: Hussain
mesh_terms: D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia; D002460:Cell Line; D018031:Connexin 43 / Q000737:chemistry / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D054086:KATP Channels / Q000737:chemistry / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
chemical_list: D018031:Connexin 43; D054086:KATP Channels; D034741:RNA, Small Interfering; C092520:uK-ATP-1 potassium channel; D045304:Cytochromes c; D051744:Protein Kinase C-epsilon
keywords: Connexin 43; Cytochrome C; Hypoxia; Kir6.1; Mitochondria; Protein kinase C