title: Connexin mediates gap junction-independent resistance to cellular injury.
abstract: Although gap junctions regulate essential processes during development and differentiation, the role of gap junctions in cell death is poorly understood. We demonstrate here that the forced expression of connexin 43 (Cx43), the main constituent of astrocytic gap junctions, protected against cell injury with a potency that was comparable with that from the expression of the proto-oncogene bcl2. The expression of two other members of the Cx family, Cx32 and Cx40, also increased the resistance to injury from exposures to calcium overload, oxidative stress, metabolic inhibition, tamoxifen, and UV irradiation, but not against staurosporine- and dexamethasone-mediated death. Surprisingly, the anti-death activity of connexin proteins was independent of gap junction channel function, because physical isolation or the pharmacological inhibition of coupling did not significantly increase cell death. Moreover, cells expressing nonfunctional mutant connexins also acquired a high resistance to injury. These observations identify Cx proteins as active players in cell survival.
authors.affiliation: Department of Pathology, New York Medical College, Valhalla, New York 10595, USA. jane_lin@nymc.edu
authors.forename: Jane H-C
authors.initials: JH
authors.lastname: Lin
authors.forename: Jay
authors.initials: J
authors.lastname: Yang
authors.forename: Shujun
authors.initials: S
authors.lastname: Liu
authors.forename: Takahiro
authors.initials: T
authors.lastname: Takano
authors.forename: Xiaohai
authors.initials: X
authors.lastname: Wang
authors.forename: Qun
authors.initials: Q
authors.lastname: Gao
authors.forename: Klaus
authors.initials: K
authors.lastname: Willecke
authors.forename: Maiken
authors.initials: M
authors.lastname: Nedergaard
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018031:Connexin 43 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D017630:Connexins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology; D017629:Gap Junctions / Q000502:physiology*; D005799:Genes, Dominant; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D051379:Mice; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D013629:Tamoxifen / Q000494:pharmacology; D014162:Transfection; D014466:Ultraviolet Rays; D000097002:Gap Junction beta-1 Protein; D000097003:Gap Junction alpha-5 Protein
chemical_list: D002118:Calcium; D018031:Connexin 43; D017630:Connexins; D004965:Estrogen Antagonists; D007476:Ionophores; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; D013629:Tamoxifen; D000097002:Gap Junction beta-1 Protein; D000097003:Gap Junction alpha-5 Protein; C000715470:MAS1 protein, human