Effects of physiological, pharmacological, and toxic factors on cell transport

Endocytic transport is a fundamental cell function involved in nutrient assimilation, signal transduction, growth, and other cellular activities. Disruption of this transport has been associated with aging and some chronic diseases. There is growing interest in possible regulation of the endocytic machinery by physiological factors, and in pathological processes. In this project, I analyzed effects of (a) pro-oxidative factors such as ROS and amyloidogenic polypeptide aggregates, (b) physiological factors such as EGF and steroid hormones, and (c) select pharmacological or phytochemical compounds, on different endocytic pathways within a cell, and among different cell types. The results provide evidence that pro-oxidants can inhibit endocytic transport in different cell types; and the pathways can exhibit differences in sensitivity to a pro-oxidant. Select physiological and pharmacological factors can also stimulate or inhibit some of these transport pathways in different cell types. Further screening and testing of pharmacological modulators may identify possible therapeutic compounds.