NUCLEAR CHOLESTEROL CONTENT AND NUCLEOSIDE TRIPHOSPHATASE-ACTIVITY ARE ALTERED IN THE JCR-LA-CP CORPULENT RAT

A nuclear pore complex-associated nucleoside triphosphatase (NTPase) a ctivity is believed to provide energy for nuclear export of poly(A)+ m RNA. This study was initiated to determine if nuclear membrane lipid c omposition is altered during chronic hyperlipidemia, and what effect t his has on NTPase activity. The JCR:LA-cp corpulent rat model is chara cterized by severe hypertriglyceridemia and moderate hypercholesterole mia, and thus represents an ideal animal model in which to study nucle ar cholesterol and NTPase activity. NTPase activity was markedly incre ased in purified hepatic nuclei from corpulent female JCR:IA-cp rats i n comparison to lean control rats as a function of assay time, [CTP], [ATP], and [Mg2+]. Nuclear membrane cholesterol and phospholipid conte nt were significantly elevated in the corpulent animals. Nuclei of cor pulent animals were less resistant to salt-induced lysis than nuclei o f lean animals, suggesting a change in relative membrane integrity. To gether, these results indicate that altered lipid metabolism in a gene tic corpulent animal model can lead to changes in nuclear membrane lip id composition, which in turn may alter nuclear membrane NTPase activi ty and integrity. (C) 1996 Wiley-Liss, Inc.