title: Acetyl-L-carnitine activates the peroxisome proliferator-activated receptor-γ coactivators PGC-1α/PGC-1β-dependent signaling cascade of mitochondrial biogenesis and decreases the oxidized peroxiredoxins content in old rat liver.
abstract: The behavior of the peroxisome proliferator-activated receptor-γ coactivators PGC-1α/PGC-β-dependent mitochondrial biogenesis signaling pathway, as well as the level of some antioxidant enzymes and proteins involved in mitochondrial dynamics in the liver of old rats before and after 2 months of acetyl-L-carnitine (ALCAR) supplementation, was tested. The results reveal that ALCAR treatment is able to reverse the age-associated decline of PGC-1α, PGC-1β, nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (TFAM), nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 1 (ND1), and cytochrome c oxidase subunit IV (COX IV) protein levels, of mitochondrial DNA (mtDNA) content, and of citrate synthase activity. Moreover, it partially reverses the mitochondrial superoxide dismutase 2 (SOD2) decline and reduces the cellular content of oxidized peroxiredoxins. These data demonstrate that ALCAR treatment is able to promote in the old rat liver a new mitochondrial population that can contribute to the cellular oxidative stress reduction. Furthermore, a remarkable decline of Drp1 and of Mfn2 proteins is reported here for the first time, suggesting a reduced mitochondrial dynamics in aging liver with no effect of ALCAR treatment.
authors.affiliation: Department of Biochemistry and Molecular Biology E. Quagliariello, University of Bari, Bari, Italy. v.pesce@biologia.uniba.it
authors.forename: Vito
authors.initials: V
authors.lastname: Pesce
authors.forename: Luigi
authors.initials: L
authors.lastname: Nicassio
authors.forename: Flavio
authors.initials: F
authors.lastname: Fracasso
authors.forename: Clara
authors.initials: C
authors.lastname: Musicco
authors.forename: Palmiro
authors.initials: P
authors.lastname: Cantatore
authors.forename: Maria Nicola
authors.initials: MN
authors.lastname: Gadaleta
mesh_terms: D000108:Acetylcarnitine / Q000378:metabolism*; D000375:Aging; D000818:Animals; D001343:Autophagy; D004272:DNA, Mitochondrial / Q000378:metabolism; D019587:Dietary Supplements; D008099:Liver / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D047495:PPAR gamma / Q000378:metabolism*; D054464:Peroxiredoxins / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D000099156:Superoxide Dismutase 2
chemical_list: D000108:Acetylcarnitine; D004272:DNA, Mitochondrial; D047495:PPAR gamma; D054464:Peroxiredoxins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins; D013482:Superoxide Dismutase; D014157:Transcription Factors; D000099156:Superoxide Dismutase 2; C501429:Ppargc1a protein, rat