AGE-RELATED-CHANGES IN THE ACTIVATION OF AORTIC CHOLESTERYL ESTER HYDROLASES BY PROTEIN-KINASES IN RATS

Age-related changes in the activities of acid and neutral cholesteryl eater hydrolases (ACEH and NCEH) and their activation by protein kinas e A (PKA) and also by protein kinase C (PKC) were examined in the aort ae of 4-, 8-, 12- and 20-week-old rats in relation to their aortic lip id and lipid peroxides and lipid contents. The physiological basal act ivity as well as total activities of the ACEH and NCEH activated by th e two kinases, which were high in the aortae of the 4- and 8-week-old rats, decreased gradually with increasing age to about 40% (ACEH) and 50% (NCEH) by 20 weeks of age. The vitamin E intake and ad libitum-die t intake of the rats each modified the age-related decline of CEH acti vities. The aortic PKA and PKC activities were reflected by the CEH ac tivities to some degree. The in vitro exposure of the aortic CEH to ac tive oxygen (AO) generators revealed the PKC-mediated activation of CE H, which was inhibited by superoxide dismutase and catalase. These res ults suggested that the activities of ACEH and NCEH and their regulato ry enzymes mag be modulated by the dual effect of endogenous AO; an ac tivation of CEH at low doses and an inactivation at high doses, or upo n a long-term exposure in aging to a low level of endogenous AO. (C) 1 998 Elsevier Science B.V.