Mechanisms of Alcohol Induced Effects on Cellular Cholesterol Dynamics

摘要

Cholesterol is important in regulation of cell structure and function. Equally important is the role that cholesterol plays in vascular disease. The focus of this grant has been on mechanisms of alcohol induced disruption of cellular cholesterol transport and distribution. We demonstrate that many of the systems involved in regulating cholesterol transport are perturbed by ethanol (HDL, apoA-I, LDL, PC-PLC, PC-PLD) . The Golgi complex plays an important role in protein and lipid trafficking and our new data confirm that the Golgi complex is perturbed by ethanol. Moreover, we are now able to measure the distribution of cholesterol in the Golgi complex and we showed that ethanol induce movement of cholesterol out of the Golgi complex with a greater effect on the cis-medial region as compared with the trans-Golgi region. Current work is elucidating the consequences of ethanol-induced cholesterol depletion in the Golgi complex on Golgi function. An overriding conclusion of the work accomplished is that ethanol at concentrations observed in problem drinkers and alcoholics (e.g., an individual consuming either 6 beers, or 6 one shots of whiskey, or 6 glasses of wine) has a profound and multifaceted effect on cellular regulation of cholesterol.