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 ester hydrolases (ACEH and NCEH) and their activation by protein kinase A (PKA) and also by protein kinase C (PKC) were examined in the aortae of 4-, 8-, 12- and 20-week-old rats in relation to their aortic lipid and lipid peroxides and lipid contents. The physiological basal activity as well as total activities of the ACEH and NCEH activated by the 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-diet intake of the rats each modified the age-related decline of CEH activities. The aortic PKA and PKC activities were reflected by the CEH activities to some degree. The in vitro exposure of the aortic CEH to active oxygen (AO) generators revealed the PKC-mediated activation of CEH, which was inhibited by superoxide dismutase and catalase. These results suggested that the activities of ACEH and NCEH and their regulatory enzymes may be modulated by the dual effect of endogenous AO; an activation of CEH at low doses and an inactivation at high doses, or upon a long-term exposure in aging to a low level of endogenous AO.