Abstract 108: Probucol Rescued Reproduction of LCAT Null Male Mice
Low plasma HDL mice, such as lecitin:cholesterol acyltransferase null mice (Lcat-null), Abca1- null mice and ABCA1 inactivator, probucol-fed mice have significantly low cholesterol content in their adrenal glands and ovaries. Cholesterylester content in brain of male LCAT null mice was significantly reduced while in female the content was not change compare to wild type mice. The reproduction of Lcat-null male pups was reduced to 31% of that expected by Mendelian genetics. Gender ratio in reproduction of wild type, ABCA1 null, and ABCG1null mice were 1 to1 in the same mating condition. Supplement of vitamin E in feeding chow increased vitamin E level in plasma and recovered reproduction defect of male LCAT null mice. Thus, plasma HDL is important lipoprotein to carry hydrophobic vitamin to steroidgenetic cells. Furthermore, although 0.2% probucol-fed mice reduced its plasma HDL only to 5% within 2 weeks, probucol-fed mice reproduced normally. This result suggesting some beneficial function may occur in this chow treatment. So that, we fed 0.2% probucol containing chow to LCAT (+/-) mice during their mating and found recovery of gender ratio in the weaned mice. HMGCoA reductase expression was increased in adrenal gland of probucol fed mice indicate cholesterol de novo synthesis may increased to support cholesterol requirement for steroid synthesis during reproduction. Probucol incorporated HDL (1.00 ug probucol / ug HDL-protein) derived probucol into NCI-H295 human adrenal cortex cell (0.73±0.12 ug probucol / mg cellular protein) and the expression of HMGCoA reductase was significantly increased compared to βactin housekeeping gene expression. Both FC and CE contents in the brain of probucol fed mice were significantly increased. Effect of probucol on cholesterol homeostasis in steroidgenic cells and neuronal cells will be examined in the future study.
- © 2013 by American Heart Association, Inc.