Identification and purification/cloning of a potent free radical scavenger from stellate cells.

Description of projects available to graduate students:
Oxidative stress-induced injury to the liver and other organs (transplantation, partial resection, and inflammation) is a major clinical challenge. Although several mechanisms of such injury have been delineated, and some antioxidants and free radical scavengers are used clinically, they have resulted in limited success. We have isolated and partially purified a protein that is secreted constitutively by the hepatic stellate cells. The protein exhibits powerful free radical scavenging activity as demonstrated by complete protection of cultured hepatocytes from reactive oxygen species (ROS)-induced death, and significant protection of the liver from ischemia/reperfusion injury in vivo. The ongoing and planned experiments are targeted to identify the protein by MALDI-MS and by conventional methods of purification and cloning of the gene. Extensive work performed in our laboratory has shown that the protein is not any of the known free radical scavenging molecules or antioxidants.

Techniques graduate student will learn:
The student will learn the techniques of isolation, purification and characterization of this protein, and its effects on free radicals-induced injury in vitro and in vivo (organ preservation, transplantation and warm ischemia/reperfusion).