The role of the P450 arachidonic acid (AA) monooxygenase as a major pathway for the metabolism of endogenous AA is now well established, as is the functional relevance of its products and of the enzymes responsible for their biosynthesis. Studies with purified proteins, genetic models of hypertension, or mice carrying disrupted P450 genes have identified members of the CYP2C and CYP4A gene subfamily of P450s as the predominant, and functionally relevant AA epoxygenase and omega hydroxylases in the rat, mouse, and human kidney, respectively. Synthetic chemistry, protein chemistry, and recombinant DNA techniques provide now efficient and routine access to most P450 eicosanoids, specific inhibitors, EET and HETE analogs, antagonists and agonist, purified P450 isoforms, P450 antibodies, cDNAs, as well as plasmid and viral vectors coding for CYP2C AA epoxygenase and CYP 4A omega-hydroxylases. In support of projects 1- 5 and, to optimize productive interactions and resources utilization. Core B will continue to apply established methods of eicosanoid extraction, purification, HPLC analysis, UPLC/MS/MS characterization, protein purification, and recombinant DNA manipulation, for: a) the detection and quantification of eicosanoids in biological samples, b) the biochemical characterization of metabolites generated by cellular, subcellular, or purified protein incubates, c) the storage, purification, and documentation of synthetic standards, specific inhibitors, agonist, and antagonists, d) the storage and documentation of immunospecific probes, e) the partial purification of recombinant enzymes, and f) the amplification, purification and documentation of cDNAs probes. The centralization of these routine tasks in Core B eliminates unnecessary and costly duplications, improves reproducibility, and provide projects 1-5 with efficient and timely access to synthetic standards, biospecific probes and state of the art bioanalytical techniques.

Public Health Relevance

Core B serves important roles in the optimization of resources, as well as a vehicle for the productive exchange of ideas and experiences. As the depository of methods and experimental tools, the Core plays an important function in facilitating interactions and promoting effort coordination among the Program Project scientists.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK038226-26
Application #
8379577
Study Section
Special Emphasis Panel (ZDK1-GRB-S)
Project Start
Project End
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
26
Fiscal Year
2012
Total Cost
$204,061
Indirect Cost
$73,141
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Garcia, Victor; Gilani, Ankit; Shkolnik, Brian et al. (2017) 20-HETE Signals Through G-Protein-Coupled Receptor GPR75 (Gq) to Affect Vascular Function and Trigger Hypertension. Circ Res 120:1776-1788
Gangadhariah, Mahesha H; Dieckmann, Blake W; Lantier, Louise et al. (2017) Cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids contribute to insulin sensitivity in mice and in humans. Diabetologia 60:1066-1075
Zhang, Hui; Falck, John R; Roman, Richard J et al. (2017) Upregulation of 20-HETE Synthetic Cytochrome P450 Isoforms by Oxygen-Glucose Deprivation in Cortical Neurons. Cell Mol Neurobiol 37:1279-1286
Guo, Zhijun; Sevrioukova, Irina F; Denisov, Ilia G et al. (2017) Heme Binding Biguanides Target Cytochrome P450-Dependent Cancer Cell Mitochondria. Cell Chem Biol 24:1259-1275.e6
Shuey, Megan M; Billings 4th, Frederic T; Wei, Shouzou et al. (2017) Association of gain-of-function EPHX2 polymorphism Lys55Arg with acute kidney injury following cardiac surgery. PLoS One 12:e0175292
Chen, Li; Joseph, Gregory; Zhang, Frank F et al. (2016) 20-HETE contributes to ischemia-induced angiogenesis. Vascul Pharmacol 83:57-65
Luther, James M; Brown, Nancy J (2016) Epoxyeicosatrienoic acids and glucose homeostasis in mice and men. Prostaglandins Other Lipid Mediat 125:2-7
Chiba, Takuto; Skrypnyk, Nataliya I; Skvarca, Lauren Brilli et al. (2016) Retinoic Acid Signaling Coordinates Macrophage-Dependent Injury and Repair after AKI. J Am Soc Nephrol 27:495-508
Hye Khan, Md Abdul; Fish, Brian; Wahl, Geneva et al. (2016) Epoxyeicosatrienoic acid analogue mitigates kidney injury in a rat model of radiation nephropathy. Clin Sci (Lond) 130:587-99
Sporkov√°, Alexandra; Reddy, Rami N; Falck, John R et al. (2016) Interlobular Arteries From 2-Kidney, 1-Clip Goldblatt Hypertensive Rats' Exhibit-Impaired Vasodilator Response to Epoxyeicosatrienoic Acids. Am J Med Sci 351:513-9

Showing the most recent 10 out of 373 publications