Preliminary Study on Clusterin Protein (sCLU) Expression in PC-12 Cells Overexpressing Wild-Type and Mutated (Swedish) AβPP genes Affected by Non-Steroid Isoprenoids and Water-Soluble Cholesterol.

摘要: In this study we attempted to verify the hypothesis that mevalonate pathway affects amyloid beta precursor protein (AβPP) processing and regulates clusterin levels. AβPP expression was monitored by green fluorescence (FL) Western blot (WB). WB showed soluble alpha (sAβPPα) presence in AβPP-wt cells Aβ AβPP-sw cells. Nerve growth factor (NGF)-differentiated rat neuronal pheochromocytoma PC-12 were untreated/treated with statins alone or together non-sterol isoprenoids. Co-treatment mevalonate, dolichol, ubiquinol, farnesol, geranylgeraniol, water-soluble cholesterol demonstrated statin-dependent neurotoxicity resulted from attenuated activity of rather than lower level. Atorvastatin (50 μM) simvastatin as well chelator methyl-β-cyclodextrin (0.2 mM) diminished cell viability (p < 0.05) Interestingly, co-treatment stimulated expression. Effects isoprenoids, but not water (Chol-PEG), most significant mock-transfected Geranylgeraniol (GGOH) overcame atorvastatin (ATR)-dependent cytotoxicity. This effect does seem be dependent on clusterin, its level became after GGOH. The novelty these findings is they show (MEV) itself plays an important role mock-transfected, AβPP-overexpressing cells, GGOH/farnesol (FOH) exerted a protective effect. Thus, prenylation GGOH/FOH might play substantial survival.