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Calcium signalling in the regulation of PGC-1alpha, PDK4 and HKII mRNA expression.

Authors: Kusuhara, K  Madsen, K  Jensen, L  Hellsten, Y  Pilegaard, H 
Citation: Kusuhara K, etal., Biol Chem. 2007 May;388(5):481-8.
Pubmed: (View Article at PubMed) PMID:17516843
DOI: Full-text: DOI:10.1515/BC.2007.052

The role of calcium signalling and specific intracellular calcium signalling pathways in regulating skeletal muscle tissue peroxisome proliferator-activated receptor gamma co-activator (PGC)-1alpha, hexokinase (HK)II and pyruvate dehydrogenase kinase (PDK)4 mRNA was examined. Cultured primary rat skeletal muscle cells were incubated for 6 h in caffeine or ionomycin. Because PGC-1alpha mRNA clearly showed greater induction with ionomycin, the latter was chosen for the main experiments, whereby cells were incubated for 6 h with either ionomycin alone or in combination with either cyclosporin A or KN-62. The PGC-1alpha mRNA level was increased (p<0.05) approximately six-fold and HKII mRNA content approximately two-fold by ionomycin relative to the corresponding controls, whereas the PDK4 mRNA content remained unaffected. Cyclosporin A abolished (p<0.05) and KN-62 reduced (p<0.1) the ionomycin-induced increase in PGC-1alpha mRNA. Electrical stimulation of in vitro incubated rat EDL muscle increased (p<0.05) PGC-1alpha mRNA by 2.2-fold after 4 h of recovery relative to a resting control, and this increase was absent when muscles were incubated with KN-62 or cyclosporin A. The present data strongly suggest that calcium signalling is involved in regulating the PGC-1alpha and HKII genes, but not PDK4. Both calcineurin and CaMK signalling seem to be involved in the calcium- and contraction-mediated PGC-1alpha up-regulation in skeletal muscle.

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CRRD Object Information
CRRD ID: 10059651
Created: 2015-08-24
Species: All species
Last Modified: 2015-08-24
Status: ACTIVE



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