Identification of a novel intracellular cholesteryl ester hydrolase (carboxylesterase 3) in human macrophages: compensatory increase in its expression after carboxylesterase 1 silencing

摘要

Several enzymes have been identified as intracellular CEHs, and whether any one of them should be considered as the major CEH is currently controversial, mainly due to the incomplete loss of activity after single gene deficiency. Gene ablation of the first candidate CEH, namely, hormone-sensitive lipase (HSL; gene: Lipe), was initially reported to have no effect on CE hydrolysis in macrophages (16), and it was concluded that HSL does not play a role in intracellular CE hydrolysis (2). Although Buchebner et al. (1) recently demonstrated a significant decrease in CE hydrolytic activity in macrophages from HSL-deficient macrophages, the observed lack of cellular CE turnover led the authors to conclude that an in vitro assay of this enzyme may not truly represent the situation in vivo. Despite the complete lack of mRNA and protein expression of the recently identified CEH KIAA1363 [also known as neutral CEH 1 (NCEH1)], macrophages from homozygous KIAA1363~(-/-) mice showed only a 40-50% reduction in total CE hydrolytic activity (no change in activity associated with the cytosolic fraction and a -30% decrease in endoplasmic reticulum-associated activity) and a corresponding 40% reduction in FC efflux (21).