UT-Houston Researchers Discover Cellular 'Lifesaver'

November 26, 1996

Media Contact: Janice Elkins
Phone: (713) 792-4257
Pager: (713) 990-2649
e-mail: jelkins@uthouston.edu

HOUSTON --(November 15, 1996)--Researchers at The University of Texas-Houston Institute of Molecular Medicine for the Prevention of Human Diseases have discovered a protein which acts as a "lifesaver" in cells about to self-destruct. The finding, reported in the Cutting Edge section of The Journal of Immunology on November 15, has important implications for the diagnosis and treatment of cardiovascular diseases, cancer and many degenerative diseases such as arthritis, multiple sclerosis and Alzheimer's disease.

Investigators led by Edward T.H. Yeh, M.D., founding director of the Institute's Cardiovascular Research Center, have named the new protein sentrin. Sentrin has been shown to block the triggers that eventually lead to the cellular changes characteristic of apoptosis (programmed cell death). The study is supported by an Established Investigator Award from the American Heart Association and a grant from the National Institutes of Health.

Dr. Yeh explains, "The protein acts as a Osentinel,' protecting cells by attaching to the cytoplasmic domain portions of Fas/APO-1 and tumor necrosis factor receptor (TNFR), molecules found at the cell surface. These receptors are known to induce the irreversible changes associated with apoptosis. A normal physiologic process that eradicates cells programmed to die, apoptosis is sometimes initiated in error, destroying healthy cells. Our research suggests that sentrin could prevent the transmission of the cell death signal by the surface molecules. Extrapolating to humans, if we can find a way to prevent cell death by apoptosis in abnormal situations, we would have a powerful weapon in the fight against many degenerative diseases."

The discovery of sentrin provides an important insight into the regulation of cell death signaling. Although more work is required before researchers are able to explain sentrin's precise mode of action, analysis has revealed that the protein is composed of 101 amino acids and is expressed in all tissues, with higher levels present in the heart, skeletal muscle, testis, ovary and thymus.

Understanding of the complex biochemical processes which determine whether cells will live or die has been greatly enlarged by the science of molecular biology. Early scholars recognized that apoptosis counterbalances cellular proliferation. For example, during embryonic development the programmed death of cells between digits ensures that webbed toes or fingers are not present at birth. Research has shown that inappropriate induction plays a central role in many pathological conditions. Dr. Yeh comments, "In such instances it may be possible to design drugs which modulate the process. If the target cells are diseased, we invoke or intensify apoptosis; if healthy, we apply therapy aimed at switching off the cell death signal."

In addition to his appointment at UT-Houston Institute of Molecular Medicine for the Prevention of Human Diseases, Dr. Yeh is director of the division of molecular medicine, department of internal medicine, UT-Houston Medical School, whose scientists collaborated on the study. He is also vice chairman in the Medical School division of cardiology. The Institute of Molecular Medicine was established in 1994 with funds totalling more than $33.3 million, over half raised from Houston area foundations, companies and individuals.

Note to editors: The paper by Yeh et al. appears in The Journal of Immunology 157(10):4277-4281, 1996.

This news release is available on World Wide Web at http://www.uth.tmc.edu/uth_orgs/pub_affairs/news.html

The University of Texas-Houston Health Science Center is dedicated to building a model health sciences center for the 21st century. It is a model built on education, research and care devoted to the maintenance of health and the prevention of disease. The University is located in the world-famous Texas Medical Center and is the state1s most comprehensive institution of health sciences.

University of Texas Health Science Center at Houston

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