Blood cellular mutant LXR-α protein stability governs initiation of coronary heart disease

Abstract

AIM:To investigate the role of [breast and ovarian cancer susceptibility 1 (BRCA1)-associated RING domain 1 (BARD1)]/BRCA1 E3-ubiquitin ligase complex in governing the stability of mutant liver X receptor-α (LXR-α) protein in coronary heart disease (CHD) subjects. METHODS:The expression analysis of various genes was carried out by quantitative real time polymerase chain reaction and western blotting within blood mononuclear cells of human CHD subjects at various stages of coronary occlusion and their corresponding normal healthy counterparts. Immunoprecipitation experiments were performed to establish protein interactions between LXR-α and BARD1. Peripheral blood mononuclear cells were cultured and exposed to Vitamin D3 and Cisplatin to validate the degradation of mutant LXR-α protein in CHD subjects by BARD1/BRCA1 complex. RESULTS:The expression of mutant LXR-α protein in CHD subjects was found to decrease gradually with the severity of coronary occlusion exhibiting a strong nega- culture experiments proved that Vitamin D3 could prevent the degradation of mutant LXR-α and restore its functional activity to some extent. BRIEF ARTICLE World Journal of CONCLUSION:Mutant LXR-α protein in CHD subjects is degraded by BARD1/BRCA1 complex and Vitamin D3 can rescue and restore its function.