The behavior of the peroxisome proliferator-activated receptor-gamma coactivators PGC-1alpha/PGC-beta—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 ageassociated decline of PGC-1alpha, PGC-1beta, 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.
Acetyl-L-Carnitine Activates the Peroxisome Proliferator-Activated Receptor-gamma Coactivators PGC-1alpha/PGC-1beta–Dependent Signaling Cascade of Mitochondrial Biogenesis and Decreases the Oxidized Peroxiredoxins Content in Old Rat Liver
PESCE, VITO;CANTATORE, Palmiro;
2012-01-01
Abstract
The behavior of the peroxisome proliferator-activated receptor-gamma coactivators PGC-1alpha/PGC-beta—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 ageassociated decline of PGC-1alpha, PGC-1beta, 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
