U18666A Inhibits Intracellular Cholesterol Transport and Neurotransmitter Release in Human Neuroblastoma Cells |
| |
Authors: | Sparrow Susan M Carter Jodi M Ridgway Neale D Cook Harold W Byers David M |
| |
Institution: | (1) Atlantic Research Centre, Departments of Pediatrics and Biochemistry, Dalhousie University, Halifax, Nova Scotia, Canada, B3H 4H7;(2) Present address: Atlantic Research Centre, Dalhousie University, Clinical Research Centre, Halifax, Nova Scotia, Canada, B3H 4H7 |
| |
Abstract: | To determine if neurochemical function might be impaired in cell models with altered cholesterol balance, we studied the effects of U18666A (3- -(2-diethyl-amino)ethoxy]androst-5-en-17-one) on intracellular cholesterol metabolism in three human neuroblastoma cell lines (SK-N-SH, SK-N-MC, and SH-SY5Y). U18666A ( 0.2 g/ml) completely inhibited low density lipoprotein (LDL)-stimulated cholesterol esterification in SK-N-SH cells, while cholesterol esterification stimulated by 25-hydroxycholesterol or bacterial sphingomyelinase was unaffected or partially inhibited, respectively. U18666A also blocked LDL-stimulated downregulation of LDL receptor and caused lysosomal accumulation of cholesterol as measured by filipin staining. U18666A treatment for 18 h resulted in 70% inhibition of K+-evoked norepinephrine release in phorbol esterdifferentiated SH-SY5Y cells, while release stimulated by the calcium ionophore A23187 was only slightly affected. These results suggest that U18666A may preferentially block a voltage-regulated Ca2+ channel involved in norepinephrine release and that alterations in neurotransmitter secretion might be a feature of disorders such as Niemann-Pick Type C, in which intracellular cholesterol transport and distribution are impaired. |
| |
Keywords: | Cholesterol U18666A neuroblastoma SH-SY5Y Niemann-Pick C disease norepinephrine |
本文献已被 SpringerLink 等数据库收录! |
|