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January 28, 2004

Death-Defying Approach Devised by Penn Scientists to Prevent Cell Apoptosis

(Philadelphia, PA) - When recovering from a heart attack or stroke, the body must restore blood flow in order to resupply cells with oxygen. Ironically, the process of reoxygenation - so necessary for full recovery - also generates reactive oxygen species (ROS), molecules that induce apoptosis, or cellular death. Now, researchers at the University of Pennsylvania School of Medicine and the University of Iowa have identified a biochemical strategy to block ROS - which effectively prevents cellular damage and death. Their study is published in February’s Proceedings of the Natural Academy of Sciences.

“We’ve known that oxidation can induce apoptosis,” said Toshinori Hoshi, PhD, Associate Professor in Penn’s Department of Physiology. “We also knew that the enzyme methionine sulfoxide reductase type A - or MSRA - is a catalyst in reversing the oxidation of the amino acid methionine, an important building block of proteins.”

After using gene-transfer technology to insert extra MRSA into cells, the researchers noticed that the enzyme-packed cells were now protected from the damaging effects of ROS. “Not only were cells protected by an overproduction of MRSA, but our tests showed that the adverse oxidation process was reversed,” explains Hoshi.

“Oxidative stress is thought to be associated with many medical conditions, such as diseases related to aging and the heart,” continues Hoshi. “Given our findings, it may be possible to prevent such stress, and thereby treat disease, by boosting the amount of MSRA in the body so its protein-repair properties are unleashed.”

This research is funded by the National Institutes of Health.

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PENN Medicine is a $2.2 billion enterprise dedicated to the related missions of medical education, biomedical research, and high-quality patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System (created in 1993 as the nation’s first integrated academic health system).

Penn’s School of Medicine is ranked #2 in the nation for receipt of NIH research funds; and ranked #4 in the nation in U.S. News & World Report’s most recent ranking of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

Penn Health System consists of four hospitals (including its flagship Hospital of the University of Pennsylvania, consistently rated one of the nation’s “Honor Roll” hospitals by U.S. News & World Report), a faculty practice plan, a primary-care provider network, three multispecialty satellite facilities, and home health care and hospice.

Release available online at http://www.uphs.upenn.edu/news/News_Releases/jan04/MSRAcall.htm