PMID- 28134630 OWN - NLM STAT- MEDLINE DCOM- 20180109 LR - 20181113 IS - 1473-558X (Electronic) IS - 0959-4965 (Print) IS - 0959-4965 (Linking) VI - 28 IP - 4 DP - 2017 Mar 1 TI - Polyamines preserve connexin 43-mediated gap junctional communication during intracellular hypercalcemia and acidosis. PG - 208-213 LID - 10.1097/WNR.0000000000000746 [doi] AB - 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. FAU - Kucheryavykh, Lilia Y AU - Kucheryavykh LY AD - Departments of aBiochemistry bPhysiology cAnatomy and Cell Biology, School of Medicine, Universidad Central del Caribe, Bayamon, 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. FAU - Benedikt, Jan AU - Benedikt J FAU - Cubano, Luis A AU - Cubano LA FAU - Skatchkov, Serguei N AU - Skatchkov SN FAU - Bukauskas, Feliksas F AU - Bukauskas FF FAU - Kucheryavykh, Yuriy V AU - Kucheryavykh YV LA - eng GR - R01 NS072238/NS/NINDS NIH HHS/United States GR - G12 MD007583/MD/NIMHD NIH HHS/United States GR - SC2 GM095410/GM/NIGMS NIH HHS/United States GR - R01 NS065201/NS/NINDS NIH HHS/United States GR - SC2 GM102040/GM/NIGMS NIH HHS/United States PT - Journal Article PL - England TA - Neuroreport JT - Neuroreport JID - 9100935 RN - 0 (Connexin 43) RN - 0 (GJA1 protein, human) RN - 0 (Polyamines) RN - 2FZ7Y3VOQX (Spermine) RN - SY7Q814VUP (Calcium) SB - IM MH - Acidosis MH - Animals MH - Calcium MH - Cell Line, Tumor MH - Connexin 43/*metabolism MH - Gap Junctions/drug effects/*physiology MH - Humans MH - Hydrogen-Ion Concentration MH - Hypercalcemia MH - Neurons/metabolism/*physiology MH - Polyamines/*administration & dosage MH - Rats MH - Spermine/administration & dosage PMC - PMC5298824 MID - NIHMS843150 COIS- Statement of conflicts of interest: none declared EDAT- 2017/01/31 06:00 MHDA- 2018/01/10 06:00 PMCR- 2018/03/01 CRDT- 2017/01/31 06:00 PHST- 2017/01/31 06:00 [pubmed] PHST- 2018/01/10 06:00 [medline] PHST- 2017/01/31 06:00 [entrez] PHST- 2018/03/01 00:00 [pmc-release] AID - 10.1097/WNR.0000000000000746 [doi] PST - ppublish SO - Neuroreport. 2017 Mar 1;28(4):208-213. doi: 10.1097/WNR.0000000000000746.