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Second low-oxygen pathway hints at cancer, cardiovascular disease physiology

Researchers at the University of Pennsylvania School of Medicine have identified a second molecular pathway that promotes cell survival in low-oxygen conditions. By teasing apart the details of cellular adaptation during oxygen deprivation, or hypoxia, the researchers hope to gain a better understanding of the abnormal hypoxic environments that are characteristic of many diseases, including solid-tumor cancers and stroke.

Oxygen sensing, the ability of a cell to gauge the oxygen concentrations in its environment and to protect itself through internal regulation, is a fundamental process in most species of animals that depend entirely on oxygen to maintain cellular function. There are multiple, oxygen-dependent pathways in the cell that are regulated by changes in oxygen levels.

By starving human cells of oxygen, Celeste Simon, PhD, Professor of Cell and Developmental Biology at Penn and a Howard Hughes Medical Institute (HHMI) Investigator, and colleagues discovered an oxygen-sensitive cellular pathway that leads to a decrease in protein synthesis. This finding is the second hypoxic cellular pathway to be identified by this research team. Simon, who is also a member of Penn's Abramson Cancer Center, and colleagues report their most recent findings in the February issue of Molecular Cell.

In order to promote cellular adaptations to hypoxia, the cell must first recognize the presence of a low-oxygen environment. Previous genetic studies from Simon's laboratory helped to establish that the mitochondriathe energy center of the cellplay a major role in oxygen sensing. Like an alarm, mitochondria alert the cells when oxygen levels fall too low, resulting in hypoxic cells activating a protein called hypoxia-inducible factor (HIF). HIF, in turn, signals for physiological changes in nearby tissue that serve to protect oxygen-deprived cells. These changes include an increase in the number of red blood cells and blood vessels, the dilation of vessels, a
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-662-2560
University of Pennsylvania School of Medicine
16-Feb-2006


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