title: Acetyl-L-carnitine feeding to unloaded rats triggers in soleus muscle the coordinated expression of genes involved in mitochondrial biogenesis.
abstract: The expressional profile of mitochondrial transcripts and of genes involved in the mitochondrial biogenesis pathway induced by ALCAR daily supplementation in soleus muscle of control and unloaded 3-month-old rats has been analyzed. It has been found that ALCAR treatment is able to upregulate the expression level of mitochondrial transcripts (COX I, ATP6, ND6, 16 S rRNA) in both control and unloaded animals. Interestingly, ALCAR feeding to unloaded rats resulted in the increase of transcript level for master factors involved in mitochondrial biogenesis (PGC-1alpha, NRF-1, TFAM). It also prevented the unloading-induced downregulation of mRNA levels for kinases able to transduce metabolic (AMPK) and neuronal stimuli (CaMKIIbeta) into mitochondrial biogenesis. No significant effect on the expressional level of such genes was found in control ALCAR-treated rats. In addition, ALCAR feeding was able to prevent the loss of mitochondrial protein content due to unloading condition. Correlation analysis revealed a strong coordination in the expression of genes involved in mitochondrial biogenesis only in ALCAR-treated suspended animals, supporting a differentiated effect of ALCAR treatment in relation to the loading state of the soleus muscle. In conclusions, we demonstrated the ability of ALCAR supplementation to promote only in soleus muscle of hindlimb suspended rats an orchestrated expression of genes involved in mitochondrial biogenesis, which might counteract the unloading-induced metabolic changes, preventing the loss of mitochondrial proteins.
authors.affiliation: Department of Biochemistry and Molecular Biology Ernesto Quagliariello, University of Bari- Via Orabona 4- 70125, Bari, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Cassano
authors.forename: A G
authors.initials: AG
authors.lastname: Sciancalepore
authors.forename: V
authors.initials: V
authors.lastname: Pesce
authors.forename: M
authors.initials: M
authors.lastname: Flück
authors.forename: H
authors.initials: H
authors.lastname: Hoppeler
authors.forename: M
authors.initials: M
authors.lastname: Calvani
authors.forename: L
authors.initials: L
authors.lastname: Mosconi
authors.forename: P
authors.initials: P
authors.lastname: Cantatore
authors.forename: M N
authors.initials: MN
authors.lastname: Gadaleta
mesh_terms: D000108:Acetylcarnitine / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D050259:Genes, Mitochondrial / Q000235:genetics*; D019417:Hindlimb Suspension / Q000502:physiology*; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000502:physiology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000235:genetics
chemical_list: D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D000108:Acetylcarnitine