A Possible Mechanism of Cholesteryl Glucoside Formation Involved in Heat Shock Response in the Animal Cell Membrane

We previously reported that cholesteryl glucoside (CG), a member of membrane glycolipid, is rapidly induced by exposure to some forms of stress in animal tissues and human cultured cells. As CO is induced by heat shock before the activation of heat shock transcription factor 1 (HSF1) and the production of heat shock protein 70 (HSP70), and CO added exogenously induces HSF1 activation and HSP70 production in animal tissue and human fibroblasts, it is suggested that CO functions as a crucial lipid mediator in cellular responses against heat stress. In this report, we showed the localization of CG synthetase, sterol glucosyltransferase, at lipid raft in the human cell membrane. Because the lipid raft is considered to be a scaffold of heat shock response leading to HSP induction, we propose that CG formation by sterol glucosyltransferase in lipid raft might act as a potential factor in the thermal sensing reaction. Additionally, using the artificial liposomes modeling on the states of membranes before and after CO production, we clarified that the transfer of the glucose moiety from glucose donor, glucosylceramide, to cholesterol changed membrane physical properties and formed thermostable solid-ordered domains. We suggest that the alteration of membrane physical state caused by heat stress might be linked to activate sterol glucosyltransferase to form CO in the animal.