title: PGC-1beta down-regulation is associated with reduced ERRalpha activity and MCAD expression in skeletal muscle of senescence-accelerated mice.
abstract: Mitochondrial dysfunction is involved in the development of aging. Here, we examined the effect of aging on the skeletal muscle expression of two isoforms of the transcriptional peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1 (PGC-1) in an experimental murine model of accelerated aging, the senescence-accelerated mouse (SAM). The senescence-accelerated prone mice (SAM-P8) showed no changes in PGC-1alpha, but a decrease in PGC-1beta expression (52% reduction, p <.001) was observed compared to the senescence-accelerated resistant mice (SAM-R1). In agreement with the proposed role of PGC-1beta as an estrogen-related receptor (ERR) protein ligand, the expression of the ERRalpha target gene medium-chain acyl-coenzyme A dehydrogenase was strongly suppressed (85%, p <.001) in SAM-P8. The decrease in the expression of medium-chain acyl-coenzyme A dehydrogenase was consistent with the reduction in ERRalpha DNA-binding activity of SAM-P8. These findings indicate that the age-mediated decrease in PGC-1beta expression in SAM-P8 skeletal muscle affects the expression of genes involved in mitochondrial fatty acid oxidation.
authors.affiliation: Unitat de Farmacologia, Facultat de Farmàcia, Diagonal 643, E-08028 Barcelona, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Rodríguez-Calvo
authors.forename: Mireia
authors.initials: M
authors.lastname: Jové
authors.forename: Teresa
authors.initials: T
authors.lastname: Coll
authors.forename: Antoni
authors.initials: A
authors.lastname: Camins
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Sánchez
authors.forename: Marta
authors.initials: M
authors.lastname: Alegret
authors.forename: Manuel
authors.initials: M
authors.lastname: Merlos
authors.forename: Mercè
authors.initials: M
authors.lastname: Pallàs
authors.forename: Juan C
authors.initials: JC
authors.lastname: Laguna
authors.forename: Manuel
authors.initials: M
authors.lastname: Vázquez-Carrera
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000378:metabolism*; D000375:Aging / Q000502:physiology*; D000818:Animals; D006801:Humans; D008297:Male; D051379:Mice; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D042964:Acyl-CoA Dehydrogenase; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1