Abstract

Arginine metabolism is profoundly altered by trauma and inflammation. The degradation of arginine by arginase is poorly understood. This application focusses on the regulation of arginine by arginase and has three aims. First, the investigator proposes to elucidate the roles of the two major isoforms, Arg I and Arg II, in the biosynthesis of NO, proline and polyamines in macrophages.
The second aim i s to elucidate the mechanisms regulating arginase expression in vivo.
The third aim i s to elucidate the physiologic roles of Arg II in vivo. The investigator will apply tools of modern molecular biology and genetics to address these questions.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057384-02
Application #
2910403
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1998-05-01
Project End
2002-04-30
Budget Start
1999-05-01
Budget End
2000-04-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Pittsburgh
Department
Genetics
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213

  Publications

Zhu, Min; Goetsch, Sean C; Wang, Zhaoning et al. (2015) FoxO4 promotes early inflammatory response upon myocardial infarction via endothelial Arg1. Circ Res 117:967-77
Zhu, Xinmei; Pribis, John P; Rodriguez, Paulo C et al. (2014) The central role of arginine catabolism in T-cell dysfunction and increased susceptibility to infection after physical injury. Ann Surg 259:171-8
Mattila, Joshua T; Ojo, Olabisi O; Kepka-Lenhart, Diane et al. (2013) Microenvironments in tuberculous granulomas are delineated by distinct populations of macrophage subsets and expression of nitric oxide synthase and arginase isoforms. J Immunol 191:773-84
You, Hanning; Gao, Ting; Cooper, Timothy K et al. (2013) Arginase inhibition mediates renal tissue protection in diabetic nephropathy by a nitric oxide synthase 3-dependent mechanism. Kidney Int 84:1189-97
Chang, Jinsam; Thangamani, Shankar; Kim, Myung H et al. (2013) Retinoic acid promotes the development of Arg1-expressing dendritic cells for the regulation of T-cell differentiation. Eur J Immunol 43:967-78
Sheldon, Kathryn E; Shandilya, Harish; Kepka-Lenhart, Diane et al. (2013) Shaping the murine macrophage phenotype: IL-4 and cyclic AMP synergistically activate the arginase I promoter. J Immunol 191:2290-8
Morris Jr, Sidney M (2012) Arginases and arginine deficiency syndromes. Curr Opin Clin Nutr Metab Care 15:64-70
Csóka, Balázs; Selmeczy, Zsolt; Koscsó, Balázs et al. (2012) Adenosine promotes alternative macrophage activation via A2A and A2B receptors. FASEB J 26:376-86
Vaisman, Boris L; Andrews, Karen L; Khong, Sacha M L et al. (2012) Selective endothelial overexpression of arginase II induces endothelial dysfunction and hypertension and enhances atherosclerosis in mice. PLoS One 7:e39487
Morris Jr, Sidney M; Gao, Ting; Cooper, Timothy K et al. (2011) Arginase-2 mediates diabetic renal injury. Diabetes 60:3015-22

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