Ye-Shih Ho, Ph.D.

Wayne State University
Professor, Institute of Environmental Health Sciences
 

Tel.

(313) 963-7660

Fax.

(313) 577- 0082

Email:

yho@wayne.edu

Address:

Institute of Environmental Health Sciences

Wayne State University
2727 Second Avenue, Room 4000
Detroit, MI 48201-2654

Overproduction of reactive oxygen species (ROS) have been implicated as important pathogenic mediators in many clinical disorders such as hyperoxic lung injury and ischemia/reperfusion- and adriamycin (ADR)-induced cardiac damage. The function of the prototypic antioxidant enzymes, which include three isoforms of superoxide dismutase, catalase, and glutathione peroxidase, in protecting cells and animals against oxidant-mediated tissue injury has been studied quite extensively both in vitro in cultured cells and in vivo in a whole animal. However, the molecular and cellular mechanisms by which ROS cause tissue injury are not well understood. In other words, the biochemical and cellular pathways, that are initiated by the increased oxidative stress in the targeted tissues and that contribute to the injury, are not known. Since sulfhydryl proteins are targets for oxidative modification when cells are under oxidative stress, and inactivation of the catalytic functions of critical cellular proteins may lead to irreversible cellular damage, we hypothesize that oxidation of sulfhydryl groups of proteins may contribute to the pathogenesis of the above three models of oxidant-mediated injury. Toward this end, the current research in our laboratory is to define the role of the cytosolic and the mitochondrial isoforms of glutaredoxin (Grx1 and Grx2, respectively), a thiotransferase functioning in reductive cleavage of protein mixed disulfides, in antioxidant defense using both transgenic and knockout mice. The potential cellular targets that interact with and that are protected by Grx1 and Grx2 will also be defined by proteomics approaches.

Fisher AB, Dodia C, Feinstein SI, Ho YS. Altered lung phospholipid metabolism in mice with targeted deletion of lysosomal-type phospholipase A2. J Lipid Res. 2005 Jun;46(6):1248-56. Epub 2005 Mar 16. PMID: 15772425

Wang Y, Feinstein SI, Manevich Y, Ho YS, Fisher AB. Lung injury and mortality with hyperoxia are increased in peroxiredoxin 6 gene-targeted mice. Free Radic Biol Med. 2004 Dec 1;37(11):1736-43. PMID: 15528033

Ho YS, Xiong Y, Ma W, Spector A, Ho DS. Mice lacking catalase develop normally but show differential sensitivity to oxidant tissue injury. J Biol Chem. 2004 Jul 30;279(31):32804-12. PMID: 15178682

Turoczi T, Chang VW, Engelman RM, Maulik N, Ho YS, Das DK. Thioredoxin redox signaling in the ischemic heart: an insight with transgenic mice overexpressing Trx1. J Mol Cell Cardiol. 2003 Jun;35(6):695-704. PMID: 12788387

Mo Y, Feinstein SI, Manevich Y, Zhang Q, Lu L, Ho YS, Fisher AB. 1-Cys peroxiredoxin knock-out mice express mRNA but not protein for a highly related intronless gene. FEBS Lett. 2003 Dec 4;555(2):192-8. PMID: 14644414

Ho YS, Vincent R, Dey MS, Slot JW, Crapo JD. Transgenic models for the study of lung antioxidant defense: enhanced manganese-containing superoxide dismutase activity gives partial protection to B6C3 hybrid mice exposed to hyperoxia. Am J Respir Cell Mol Biol. 1998 Apr;18(4):538-47. PMID: 9533942

Ho YS, Gargano M, Cao J, Bronson RT, Heimler I, Hutz RJ. Reduced fertility in female mice lacking copper-zinc superoxide dismutase. J Biol Chem. 1998 Mar 27;273(13):7765-9. PMID: 9516486

Ho YS, Magnenat JL, Bronson RT, Cao J, Gargano M, Sugawara M, Funk CD. Mice deficient in cellular glutathione peroxidase develop normally and show no increased sensitivity to hyperoxia. J Biol Chem. 1997 Jun 27;272(26):16644-51. PMID: 9195979