title: Senescence-associated decline in hepatic peroxisomal enzyme activities corresponds with diminished levels of retinoid X receptor alpha, but not peroxisome proliferator-activated receptor alpha.
abstract: Aging is associated with alterations in hepatic peroxisomal metabolism and susceptibility to hepatocarcinogenicity produced by agonists of peroxisome proliferator-activated receptor alpha (PPAR alpha). Mechanisms involved in these effects are not well understood. However, as a heterodimer with retinoid X receptor alpha (RXR alpha), PPAR alpha 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 apoptosis, and peroxisomal beta-oxidation activity, a major source of H(2)O(2), 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 PPAR alpha and RXR alpha in these animals. Data show that peroxisomal beta-oxidation and catalase activities were significantly lower in livers of the 100 week old animals compared with other age groups, while percentage of apoptotic hepatocytes were identical in all animal age groups. However, aging had no effect on hepatic PPAR alpha protein levels. In the senescent 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 RXR alpha 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 RXR alpha receptor, and not the primary PPAR alpha receptor. On the other hand, PPAR alpha-independent mechanisms appear to play a role in controlling apoptosis in the senescent liver.
authors.affiliation: University of Missouri-Kansas City, 2411 Holmes Street, M3-115, Kansas City, MO 64108-2792, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Chao
authors.forename: Jihan
authors.initials: J
authors.lastname: Youssef
authors.forename: Mohammad
authors.initials: M
authors.lastname: Rezaiekhaleigh
authors.forename: Linda S
authors.initials: LS
authors.lastname: Birnbaum
authors.forename: Mostafa
authors.initials: M
authors.lastname: Badr
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D017209:Apoptosis; D002374:Catalase / Q000378:metabolism; D022781:Hepatocytes / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000201:enzymology*; D051381:Rats; D011916:Rats, Inbred F344; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D002374:Catalase