title: Hyperthermia differently affects connexin43 expression and gap junction permeability in skeletal myoblasts and HeLa cells.
abstract: Stress kinases can be activated by hyperthermia and modify the expression level and properties of membranous and intercellular channels. We examined the role of c-Jun NH2-terminal kinase (JNK) in hyperthermia-induced changes of connexin43 (Cx43) expression and permeability of Cx43 gap junctions (GJs) in the rabbit skeletal myoblasts (SkMs) and Cx43-EGFP transfected HeLa cells. Hyperthermia (42°C for 6 h) enhanced the activity of JNK and its target, the transcription factor c-Jun, in both SkMs and HeLa cells. In SkMs, hyperthermia caused a 3.2-fold increase in the total Cx43 protein level and enhanced the efficacy of GJ intercellular communication (GJIC). In striking contrast, hyperthermia reduced the total amount of Cx43 protein, the number of Cx43 channels in GJ plaques, the density of hemichannels in the cell membranes, and the efficiency of GJIC in HeLa cells. Both in SkMs and HeLa cells, these changes could be prevented by XG-102, a JNK inhibitor. In HeLa cells, the changes in Cx43 expression and GJIC under hyperthermic conditions were accompanied by JNK-dependent disorganization of actin cytoskeleton stress fibers while in SkMs, the actin cytoskeleton remained intact. These findings provide an attractive model to identify the regulatory players within signalosomes, which determine the cell-dependent outcomes of hyperthermia.
authors.affiliation: Institute of Cardiology, Lithuanian University of Health Sciences, Sukilėli ų Avenue 17, 50009 Kaunas, Lithuania.
authors.forename: Ieva
authors.initials: I
authors.lastname: Antanavičiūtė
authors.affiliation: Institute of Cardiology, Lithuanian University of Health Sciences, Sukilėli ų Avenue 17, 50009 Kaunas, Lithuania ; Faculty of Natural Sciences, Vytautas Magnus University, 44404 Kaunas, Lithuania.
authors.forename: Vida
authors.initials: V
authors.lastname: Mildažienė
authors.affiliation: Institute of Physiology and Pharmacology, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania.
authors.forename: Edgaras
authors.initials: E
authors.lastname: Stankevičius
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Kiel University, Hospitalstraße 4, 24105 Kiel, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Herdegen
authors.affiliation: Institute of Cardiology, Lithuanian University of Health Sciences, Sukilėli ų Avenue 17, 50009 Kaunas, Lithuania ; Institute of Physiology and Pharmacology, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania.
authors.forename: Vytenis Arvydas
authors.initials: VA
authors.lastname: Skeberdis
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability / Q000502:physiology*; D018031:Connexin 43 / Q000378:metabolism*; D005260:Female; D005334:Fever / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D032448:Myoblasts, Skeletal / Q000378:metabolism*; D011817:Rabbits
chemical_list: D018031:Connexin 43