PMID- 17516843 OWN - NLM STAT- MEDLINE DCOM- 20070608 LR - 20161124 IS - 1431-6730 (Print) IS - 1431-6730 (Linking) VI - 388 IP - 5 DP - 2007 May TI - Calcium signalling in the regulation of PGC-1alpha, PDK4 and HKII mRNA expression. PG - 481-8 AB - 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. FAU - Kusuhara, Keiko AU - Kusuhara K AD - Copenhagen Muscle Research Centre and Centre of Inflammation and Metabolism, The August Krogh Building, Department of Molecular Biology, University of Copenhagen, Copenhagen O, Denmark. FAU - Madsen, Klavs AU - Madsen K FAU - Jensen, Lotte AU - Jensen L FAU - Hellsten, Ylva AU - Hellsten Y FAU - Pilegaard, Henriette AU - Pilegaard H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Biol Chem JT - Biological chemistry JID - 9700112 RN - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha) RN - 0 (Ppargc1a protein, rat) RN - 0 (RNA, Messenger) RN - 0 (RNA-Binding Proteins) RN - 0 (Transcription Factors) RN - 3G6A5W338E (Caffeine) RN - 56092-81-0 (Ionomycin) RN - 63HM46XPOW (KN 62) RN - 83HN0GTJ6D (Cyclosporine) RN - 84477-87-2 (1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.1.- (pyruvate dehydrogenase kinase 4) RN - EC 2.7.1.1 (Hexokinase) SB - IM MH - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives/pharmacology MH - Animals MH - Caffeine/pharmacology MH - *Calcium Signaling MH - Cells, Cultured MH - Cyclosporine/pharmacology MH - Electric Stimulation MH - Gene Expression Regulation/drug effects/*genetics MH - Hexokinase/classification/genetics/*metabolism MH - Ionomycin/pharmacology MH - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha MH - Protein Kinases/genetics/*metabolism MH - RNA, Messenger/genetics MH - RNA-Binding Proteins/genetics/*metabolism MH - Rats MH - Rats, Wistar MH - Transcription Factors/genetics/*metabolism EDAT- 2007/05/23 09:00 MHDA- 2007/06/09 09:00 CRDT- 2007/05/23 09:00 PHST- 2007/05/23 09:00 [pubmed] PHST- 2007/06/09 09:00 [medline] PHST- 2007/05/23 09:00 [entrez] AID - 10.1515/BC.2007.052 [doi] PST - ppublish SO - Biol Chem. 2007 May;388(5):481-8. doi: 10.1515/BC.2007.052.