Receptor That Protects Mice from Toxic Overload May Hold Key to Cholesterol-Related Illnesses in Humans.News Editors & Health/Medical Writers LOS ANGELES--(BUSINESS WIRE)--Feb. 4, 2003 Research published today in Proceedings of the National Academy of Sciences The Proceedings of the National Academy of Sciences of the United States of America, usually referred to as PNAS, is the official journal of the United States National Academy of Sciences. suggests that a receptor in the cells of mice that protects them from toxins may hold a key to understanding and treating cholesterol-related illnesses in humans. Pregnane X receptor In molecular biology, the pregnane X receptor (PXR) is a nuclear receptor whose primary function is to sense the presence of foreign toxic substances and in response up regulate the expression of proteins involved in the detoxification and clearance of these substance from , or PXR, is present in humans but does not recognize or eliminate all toxins as effectively as it does in our diminutive counterparts. In mice, PXR senses the presence of excess cholesterol by-products and immediately activates special pathways that remove these toxins. "PXR essentially acts like a sophisticated biological smoke detector. It knows when there is smoke and calls in the fire engines," says Barry Forman, M.D., Ph.D., associate professor, Molecular Medicine, City of Hope National Medical Center City of Hope is one of 39 NCI-designated Cancer Centers and is located in the city of Duarte, California. City of Hope comprises an ambulatory and in-patient cancer treatment center as well as a biomedical research facility known as the Beckman Research Institute and the City of Hope and Beckman Research Institute The Beckman Research Institute (BRI) is a research facility affiliated with the City of Hope National Medical Center in Duarte, CA. It is dedicated to studying normal and abnormal biological processes which may be related to cancer. and City of Hope Gonda Diabetes Center. "This important mechanism protects mice from the often severe effects suffered by patients with high levels of certain cholesterol by-products or metabolites." The central problem in humans is that the PXR receptor is not activated by the metabolites to trigger an effective response and clear away the cholesterol. The discovery came in a study of Cerebrotendinous Xanthomatosis, or CTX, a rare and often fatal disorder caused by excessive cholesterol metabolites. Less than 100 people in the United States suffer from CTX, but harnessing PXR could benefit not only those patients but also millions of people with high cholesterol worldwide. High cholesterol is a leading cause of heart disease, the #1 cause of death in the U.S., as well as strokes. The research further suggests that CTX and other cholesterol-related illnesses could be treated or possibly even prevented with existing drugs that do activate the PXR receptor in humans. These drugs include rifampicin and St. John's Wort St. John’s wort indicates animosity. [Flower Symbolism: Flora Symbolica, 177] See : Hatred St. John’s wort defense against fairies, evil spirits, the Devil. [Br. , an over-the-counter herbal agent. Future studies are needed to determine whether these drugs can remove cholesterol metabolites in CTX patients or in individuals with high cholesterol. Co-investigators include Isabelle Dussault, Ph.D., Hye-Dong Yoo, Ph.D., Min Lin, M.S., Eric Wang; B.S. and Ming Fan, M.S., all of City of Hope; Ashok K. Batta, Ph.D. and Gerald Salen, M.D., both of New Jersey Medical School, Newark, and Veterans Affairs Medical Center, East Orange, N.J.; and Sandra K. Erickson, Ph.D., University of California The University of California has a combined student body of more than 191,000 students, over 1,340,000 living alumni, and a combined systemwide and campus endowment of just over $7.3 billion (8th largest in the United States). and Veterans Affairs Medical Center, San Francisco. The scientific abstract entitled "Identification of an endogenous ligand that activates pregnane X receptor-mediated sterol Sterol Any of a group of naturally occurring or synthetic organic compounds with a steroid ring structure, having a hydroxyl (—OH) group, usually attached to carbon-3. clearance" is available in the current edition of the journal or on-line at http://www.pnas.org/cgi/content/abstract/0236235100v1. City of Hope National Medical Center and Beckman Research Institute is one of the world's leading research and treatment centers for cancer and other life-threatening diseases, including diabetes and HIV/AIDS HIV/AIDS Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome . A pioneer in the fields of bone marrow transplantation Bone Marrow Transplantation Definition The bone marrow—the sponge-like tissue found in the center of certain bones—contains stem cells that are the precursors of white blood cells, red blood cells, and platelets. and genetics, City of Hope is a National Cancer Institute-designated Comprehensive Cancer Center. For more information, visit www.cityofhope.org. |
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