AGE-RELATED AND SEX-RELATED DIFFERENCES IN NUCLEAR LIPID-CONTENT AND NUCLEOSIDE TRIPHOSPHATASE-ACTIVITY IN THE JCR-LA-CP CORPULENT RAT

The putative role of the nuclear nucleoside triphosphatase (NTPase) is to provide energy to the nuclear pore complex for poly A(+) mRNA expo rt. Previous work has demonstrated that liver nuclear NTPase activity is greater in 6 month old corpulent (cp/cp) female JCR:LA rats, a hype rlipidemic rat model, compared to lean (+/?) animals. This increase ap peared to be related to increases in nuclear membrane cholesterol cont ent. The current study extended these initial data to compare NTPase a ctivity as a function of age and sex in isolated JCR:LA-cp rat liver n uclei, to further test the hypothesis that nuclear membrane cholestero l may modulate NTPase activity. NTPase activity was increased in cp/cp female animals compared to +/? females at all ages studied, with V-ma x values increased by 60-176%. Membrane integrity of cp/cp female nucl ei was reduced compared to +/? female nuclei. Nuclear membrane cholest erol levels increased linearly with age by 50, 150 and 250% in 3, 6 an d 9 month old cp/cp females over leans. In contrast, nuclei from cp/cp males exhibited only minor, isolated changes in NTPase activity. Furt hermore, there were no significant changes in nuclear cholesterol cont ent or membrane integrity in the less hyperlipidemic male animals at a ny age. These data suggest that altered lipid metabolism may lead to c hanges in nuclear membrane structure, which in turn may alter NTPase a ctivity and functioning of the nuclear pore complex.