Cell Survival When Deprived of Oxygen

Hypoxia is a condition whereby cells and tissues become severely deprived of oxygen. In humans it can happen during many disease states such as heart failure, stroke and cancer. During these times the body is able to suppress non-essential activities to conserve oxygen. How it does this is something of a mystery.

Researchers from the University of California, San Diego School of Medicine, have identified a genetic switch in fruit flies that enables cells to survive low oxygen levels.

The fruit fly was studied because the basic genetics and cellular mechanisms of fruit fly and human are very similar.

To carry out their research the scientists developed a strain of Drosophila melanogaster that was tolerant to hypoxic conditions. Then they studied about 13,000 genes and compared these with the genomes of normal fruit flies. They were on the lookout for changes in the basic genetics of the hypoxic fruit flies i.e. any genes that might be activated or suppressed during severe hypoxia.

These genetic profiles were then compared with normal Drosophila melanogaster to look at the difference in expression patterns.

In all, more than 13,000 (about 90 per cent) of the known genes in the fly genome were studied.

The gene that looked the most promising was called the hairy gene. The scientists noted that it binds to and shuts off or suppresses the activation of many genes and signalling pathways. By doing this it allows the cells to become resistant to a low oxygen environment, they are somehow able to conserve power.

"When hairy is activated, it puts the brakes on various signaling pathways in the cell, enabling the cells to become resistant to the low-oxygen environment." That's the view of Gabriel G. Haddad, M.D., Professor of Pediatrics and Neurosciences, Chair of Pediatrics at UC San Diego School of Medicine and Physician-in-Chief at the Rady Children's Hospital, San Diego.

The scientists believe that there are many pathways involved in tolerance to low oxygen environments, but the one involving the hairy gene is critical.

By knowing more about what happens in hypoxic cells in fruit flies, it's hoped that the knowledge can be applied to help human cells and tissue survive in low oxygen conditions caused by disease.

UC San Diegio Press Center http://ucsdnews.ucsd.edu/newsrel/health/10-08Hypoxia.asp