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SENESCENCE-ASSOCIATED DECLINE IN HEPATIC PEROXISOMAL ENZYME ACTIVITIES CORRESPONDS WITH DIMINISHED LEVELS OF RETINOID X RECEPTOR ALPHA, BUT NOT PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR ALPHA1
Citation:
Chao, C., M. Rezaiekhaleigh, L S. Birnbaum, AND M. Z. Badr. SENESCENCE-ASSOCIATED DECLINE IN HEPATIC PEROXISOMAL ENZYME ACTIVITIES CORRESPONDS WITH DIMINISHED LEVELS OF RETINOID X RECEPTOR ALPHA, BUT NOT PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR ALPHA1. MECHANISMS OF AGEING AND DEVELOPMENT 123:1469-1476.
Description:
Abstract
Aging is associated with alterations in hepatic peroxisomal metabolism and susceptibility to hepatocarcinogenecity produced by agonists of peroxisome proliferator-activated receptor alpha (PPARa). Mechanisms involved in these effects are not well understood. However, as a heterodimer with retinoid X receptor alpha (RXRa), PPARa regulates transcription of genes involved in oxidative stress, cell proliferation and apoptosis. Modulating these important cell functions as a result of aging may be responsible for altered hepatic peroxisomal responses in the senescent liver. Therefore, we investigated hepatic peroxisomal b-oxidation activity, a major source of H2O2, as well as the activity of the peroxisomal anti-oxidant enzyme catalase, in male Fischer-344 rats of four age groups (4, 10, 50 and 100 week old). We further quantified protein levels of both PPARa and RXRa in these animals. Data show that peroxisomal b-oxidation and catalase activities were significantly lower in livers of the100 week old animals. However, aging had no effect on hepatic PPARa protein levels. In the senescent animal group, the level of decline in both peroxisomal enzyme activities of 30% was surprisingly similar to the decline observed in the hepatic expression of the RXRa protein. Results from this study suggest that alterations in peroxisomal metabolism observed in the senescent liver may be a result of the decline in the availability of RXRa receptor, and not the primary PPARa receptor.
Key Words: Peroxisome-proliferator activated receptors, retinoic X receptors, aging, peroxisomal b-oxidation.