title: Polyamines preserve connexin 43-mediated gap junctional communication during intracellular hypercalcemia and acidosis.
abstract: Changes in the regulation, formation, and gating of connexin-based gap junction channels occur in various disorders. It has been shown that H and Ca are involved in the regulation of gap junctional communication. Ischemia-induced intracellular acidification and Ca overload lead to closure of gap junctions and inhibit an exchange by ions and small molecules throughout the network of cells in the heart, brain, and other tissues. In this study, we examined the role of the polyamines in the regulation of connexin 43 (Cx43)-based gap junction channels under elevated intracellular concentrations of hydrogen ([H]i) and calcium ([Ca]i) ions. Experiments, conducted in Novikoff and A172 human glioblastoma cells, which endogenously express Cx43, showed that polyamines prevent downregulation of Cx43-mediated gap junctional communication caused by elevated [Ca]i and [H]i, accompanying ischemic and other pathological conditions. siRNA knockdown of Cx43 significantly reduces gap junctional communication, indicating that Cx43 gap junctions are the targets for spermine regulation.
authors.affiliation: Departments of aBiochemistry bPhysiology cAnatomy and Cell Biology, School of Medicine, Universidad Central del Caribe, Bayamón, Puerto Rico dDominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, New York, USA eInstitute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Lilia Y
authors.initials: LY
authors.lastname: Kucheryavykh
authors.forename: Jan
authors.initials: J
authors.lastname: Benedikt
authors.forename: Luis A
authors.initials: LA
authors.lastname: Cubano
authors.forename: Serguei N
authors.initials: SN
authors.lastname: Skatchkov
authors.forename: Feliksas F
authors.initials: FF
authors.lastname: Bukauskas
authors.forename: Yuriy V
authors.initials: YV
authors.lastname: Kucheryavykh
mesh_terms: D000138:Acidosis; D000818:Animals; D002118:Calcium; D045744:Cell Line, Tumor; D018031:Connexin 43 / Q000378:metabolism*; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006934:Hypercalcemia; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D011073:Polyamines / Q000008:administration & dosage*; D051381:Rats; D013096:Spermine / Q000008:administration & dosage
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human; D011073:Polyamines; D013096:Spermine; D002118:Calcium