October 20, 2005 Source: University of Calgary: http://www.ucalgary.ca/news/oct05/cholesterol-a-break.html Give cholesterol a break! U of C team discovers cholesterol performs two positive roles The October issue of the Journal of Cell Science features insights into cholesterol uncovered by a U of C team which indicate that cholesterol may not fully deserve its nasty reputation. The paper titled, Cholesterol facilitates the native mechanism of Ca2+-triggered membrane fusion, shows that cholesterol has two positive roles in regulated secretion. Cholesterol acts as an organizer of lipid rafts, expediting fusion by keeping critical components together. "It’s essentially a molecular socializer," says Jens Coorssen, PhD, associate professor of physiology and biophysics at U of C’s Faculty of Medicine. By virtue of its molecular shape (negative curvature), cholesterol also works in concert with protein factors to support speedy calcium-regulated membrane fusion. Triggered fusion is the defining step of secretion, enabling the release of compounds from specialized cells. This includes the release of neurotransmitters essential to brain function, and the secretion of insulin from pancreatic cells. "The discovery that cholesterol, a fundamental building block in cell membranes, controls regulated secretion will be of importance in future studies of cell physiology," says Leonid Chernomordik, PhD, National Institute of Child Health and Human Development, National Institutes of Health. "It may also help in the search for new approaches in treating cholesterol-related diseases." Coorssen’s team is using a model system of secretory vesicles isolated from sea urchin eggs, and integrated lipid and proteomic analyses to dissect this fundamental cellular mechanism. "The results of this research are consistent with some side-effects seen in people being treated for high cholesterol," says Coorssen, a member of the Hotchkiss Brain Institute, University of Calgary / Calgary Health Region. "These findings suggest that the widespread use of conventional anti-cholesterol treatments may need to be reconsidered in terms of more individualized dosages". This discovery is expected to prompt further study regarding cholesterol’s interaction with other molecules. It may lead to improved treatments for atherosclerosis and a variety of cognitive disorders. This study is supported by the Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council, and Alberta Heritage Foundation for Medical Research. The equipment was purchased with a Canadian Foundation for Innovation grant. Matthew Churchward, MSc graduate student, Tatiana Rogasevskaia, PhD, research associate, and Jason Bau, Bachelor of Health Sciences student, all at U of C, and Jana Höfgen, visiting graduate student from the University of Munich were co-authors on the paper. For more information: Jens Coorssen, PhD, at jcoorsse@ucalgary.ca
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