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This Article Full Text Full Text (PDF) All Versions of this Article: 576/2/391    most recent jphysiol.2006.115006v2 jphysiol.2006.115006v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Alfieri, R. R. Articles by Petronini, P. G. Search for Related Content PubMed PubMed Citation Articles by Alfieri, R. R. Articles by Petronini, P. G. Related Collections Cellular

Dipartimenti di
¹ Medicina Sperimentale, Sezione di Patologia Molecolare e Immunologia
² Clinica Medica, Nefrologia e Scienze della Prevenzione
³ Farmaceutico, Universitá degli Studi di Parma, 43100 Parma, Italy
⁴ Dipartimento di Patologia Sperimentale, Università degli Studi di Bologna, 40126 Bologna, Italy
⁵ Istituto di Farmacologia e Farmacognosia, Università degli Studi di Urbino ‘Carlo Bo’, 61029 Urbino, Italy
⁶ Department of Biochemistry, School of Life Sciences, JMS Building, University of Sussex, Brighton BN1 9QG, UK

Exposure of C2C12 muscle cells to hypertonic stress induced an increase in cell content of creatine transporter mRNA and of creatine transport activity, which peaked after about 24 h incubation at 0.45 osmol (kg H₂O)^–1. This induction of transport activity was prevented by addition of either cycloheximide, to inhibit protein synthesis, or of actinomycin D, to inhibit RNA synthesis. Creatine uptake by these cells is largely Na⁺ dependent and kinetic analysis revealed that its increase under hypertonic conditions resulted from an increase in V_max of the Na⁺-dependent component, with no significant change in the K_m value of about 75 µmol l^–1. Quantitative real-time PCR revealed a more than threefold increase in the expression of creatine transporter mRNA in cells exposed to hypertonicity. Creatine supplementation significantly enhanced survival of C2C12 cells incubated under hypertonic conditions and its effect was similar to that obtained with the well known compatible osmolytes, betaine, taurine and myo-inositol. This effect seemed not to be linked to the energy status of the C2C12 cells because hypertonic incubation caused a decrease in their ATP content, with or without the addition of creatine at 20 mmol l^–1 to the medium. This induction of creatine transport activity by hypertonicity is not confined to muscle cells: a similar induction was shown in porcine endothelial cells.

(Received 9 June 2006; accepted after revision 24 July 2006; first published online 27 July 2006)
Corresponding author K. P. Wheeler: Department of Biochemistry, School of Life Sciences, JMS Building, University of Sussex, Brighton BN1 9QG, UK. Email: k.p.wheeler{at}sussex.ac.uk

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