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This Article Full Text Full Text (PDF) All Versions of this Article: 297/3/C581    most recent 00167.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Jorquera, G. Articles by Riveros, N. PubMed PubMed Citation Articles by Jorquera, G. Articles by Riveros, N.

MUSCLE CELL BIOLOGY AND CELL MOTILITY

Membrane depolarization induces calcium-dependent upregulation of Hsp70 and Hmox-1 in skeletal muscle cells

Gonzalo Jorquera, Nevenka Jureti, Enrique Jaimovich, and Nora Riveros

Centro de Estudios Moleculares de la Célula, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago 7, Chile

Submitted 20 April 2009 ; accepted in final form 29 June 2009

Heat shock proteins (HSPs) are a conserved family of cytoprotective polypeptides, synthesized by cells in response to stress. Hsp70 and heme oxygenase 1 (Hmox-1) are induced by a variety of cellular stressors in skeletal muscle, playing a role in long-term adaptations and muscle fibers regeneration. Though HSPs expression after exercise has been intensely investigated, the molecular mechanisms concerning Hsp70 and Hmox-1 induction are poorly understood. The aim of this work was to investigate the involvement of calcium in Hsp70 and Hmox-1 expression upon depolarization of skeletal muscle cells. We observed that depolarization of myotubes increased both mRNA levels and protein expression for Hsp70 and Hmox-1. Stimulation in the presence of intracellular calcium chelator BAPTA-AM resulted in a complete inhibition of Hsp70-induced expression. It is known that inositol-1,4,5-trisphophate (IP₃)-mediated slow Ca²⁺ transients, evoked by membrane depolarization, are involved in the regulation of gene expression. Here we demonstrated that inhibition of IP₃-dependent calcium signals decreased both Hsp70 mRNA induction and Hsp70 and Hmox-1 protein expression. Inhibitors of calcium-dependent protein kinase C also abolished Hsp70 mRNA induction. Our results provide evidence that membrane depolarization increases Hsp70 and Hmox-1 expression in cultured skeletal muscle cells, which the effect is critically dependent on Ca²⁺ released from IP₃-sensitive intracellular stores and that it involves PKC as an upstream effector in Hsp70 mRNA-induced expression.

myotubes; excitation-transcription; inositol-1,4,5-trisphophate receptors; heat shock proteins; muscle gene expression