Hyperthermia Differently Affects Connexin43 Expression and Gap Junction Permeability in Skeletal Myoblasts and HeLa Cells

• Published in: Mediators of Inflammation Vol. 2014; no. 7; pp. 375 - 390
• Main Authors: Herdegen, Thomas, Stankevičius, Edgaras, Mildažienė, Vida, Antanavičiūtė, Ieva, Skeberdis, Vytenis Arvydas
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Limiteds 01-01-2014; Hindawi Publishing Corporation; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Animals; Cell Membrane Permeability - physiology; Connexin 43 - metabolism; Female; Fever; Fever - metabolism; Gap Junctions - metabolism; Gene expression; Genetic aspects; Health aspects; HeLa Cells; Humans; Hyperthermia; Identification and classification; Immunohistochemistry; In Vitro Techniques; Male; Muscle cells; Myoblasts, Skeletal - metabolism; Rabbits
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2014/748290

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.