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KillerRed: The Hypoxia Connection

A few days ago I blogged on linkurl:a new fluorescent protein;http://www.the-scientist.com/blog/display/22976/ called KillerRed. Upon irradiation with green light KillerRed produces reactive oxygen species in sufficient quantities to kill both prokaryotic and eukaryotic cells. The authors suggest several potential applications, but I?ve come up with another: hypoxia research. Before I joined __The Scientist__ I was a postdoc in Celeste Simon's lab at the University of Pennsylvania. Simon works

By | January 25, 2006

A few days ago I blogged on linkurl:a new fluorescent protein;http://www.the-scientist.com/blog/display/22976/ called KillerRed. Upon irradiation with green light KillerRed produces reactive oxygen species in sufficient quantities to kill both prokaryotic and eukaryotic cells. The authors suggest several potential applications, but I?ve come up with another: hypoxia research. Before I joined __The Scientist__ I was a postdoc in Celeste Simon's lab at the University of Pennsylvania. Simon works on the hypoxic response, that is, how cells respond to low oxygen conditions. A key player in the hypoxic response are the linkurl:HIF (hypoxia-inducible factor);http://www.the-scientist.com/article/display/15063/ proteins, a family of oxygen-regulated transcription factors. In a series of three papers published in __Cell Metabolism__ this past June, Simon, along with Paul Schumacker of the University of Chicago and Navdeep Chandel of Northwestern University Medical School, "establish that ROS produced by mitochondria are required for the normal induction of HIF, which is a master regulator of oxygen-sensitive gene expression, by low oxygen," according to linkurl:Bill Kaelin?s summary;http://www.cellmetabolism.org/content/article/abstract?uid=PIIS1550413105001440 of the three papers. If KillerRed's ROS production could be tweaked (either by varying light exposure or genetic modification), it might become a valuable tool to recapitulate or stimulate the hypoxic response without requiring either a hypoxic chamber or chemical treatments. But, Simon cautions, "there?s a lot of hypoxic responses that aren?t downstream of ROS." And ROS have other effects, including induction of Ras, NF-kappaB, and DNA damage, she says. Simon?s conclusion: If you want to study HIF activation, stick with desferrioxamine or cobalt chloride. "It would be great for studying redox changes in the cell, but I'd be cautious before using it as a mimetic for true hypoxia."
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