Calcineurin and heat-shock proteins modulation in clenbuterol-induced hypertrophied rat skeletal muscles.

Abstract

To examine the changes in heat shock proteins (HSPs) and calcineurin (CaN), a calcium/calmodulin regulated protein phosphatase, in hypertrophied rat skeletal muscles, adult male Wistar rats were administered clenbuterol (CLB, 30 mg l(-1) in drinking water), a beta 2-agonist, for 4 weeks. Compared to controls, CLB-treated rats had significantly larger body (10%) and relative (to body weight) soleus (Sol, 16%), plantaris (Plt, 32%) and gastrocnemius (Gast, 27%) weights. Immunohistochemically classified fast fibers were hypertrophied in the Sol (64%), Plt (62%), and deep (d, 70%) and superficial (s, 44%) regions of the Gast, whereas slow fibers were hypertrophied only in the Plt (47%). The percentage of fast fibers in the Sol increased from 10% to 21%. The myosin heavy chain (MHC) isoform composition shifted from slow to fast in the Sol (increase in the percentage of type IIa MHC and de novo synthesis of type IIx MHC) and Gast-d (de novo synthesis of type IIb MHC) and to the faster isoforms in the Plt (increase in the percentage of type IIb MHC). Hsp72 and Hsp90 levels in CLB-treated rats were 52% and 50% lower in the Sol and 44 and 41% lower in the Gast-d, respectively, than in control rats. In control rats, the relative content of CaN was: Sol>Gast-d>Plt>Gast-s, and CLB treatment enhanced the CaN content by 1.4-, 1.2-, 5.0-, and 3.3-fold, respectively. These results indicate that the down-regulation of HSPs in the Sol and Gast-d was closely related to a decrease in the slow phenotype, and that the relative up-regulation of CaN among the muscles/regions was closely related to the selective hypertrophy of fast fibers in the CLB-treated rats.