The CYP-derived eicosanoids including EETs and 20-HETE are at the center of the proposed research in each project of this Program Project. Accordingly, a centralized core facility to measure their levels in tissues and biological fluids is critical for the execution and successful completion of the proposed studies. Mass spectrometry remains the state-of-the art methodology for quantitative analysis of eicosanoids and their derivatives as well as for structural identification of new lipid molecules. The centralized Mass Spectroscopy Core will continue to provide investigators in this program with a consolidated, highly specialized, well equipped and professionally staffed unit capable of performing a variety of mass spectroscopy-based analyses of various eicosanoids, including advanced liquid chromatography-tandem mass spectrometry (LC/MS/MS) and gas chromatography-mass spectrometry (GC/MS). This centralized core facility ensures uniformity of assay results between the different projects while maintaining the highest quality of analytical precision and accuracy achievable;it will keep complete, computerized and centralized records as well as well-defined quality control guidelines for each method. Consequently, the specific objectives of the Core are: 1) To establish and ensure uniform standardized methods for preparing samples for analyses including sample collection, extraction and storage till analyses;2) To provide reliable, reproducible and timely mass spectroscopy analyses of CYP-derived eicosanoids in tissues and biological fluids (plasma, urine, etc.);3) To maintain computerized records of raw data and analyzed results;4)To assist investigators in developing new methods. Utilization of mass spectrometry at many levels is an important feature ofthis Program Project proposal. This stems from the recognition that mass spectrometric analyses provide adequate sensitivity, specificity, and selectivity required for detection and characterization of subpicomolar quantities of eicosanoids. No other technique of comparable sensitivity is currently available for their characterization and quantification. All Program Project Investigators will utilize the mass spectrometry for one or more aspects of quantitative, structural and chiral analyses.

Public Health Relevance

(See inslructions): The ability to identify, detect and quantify CYP-eicosanoids and related metabolites in tissues, cells and biological fluids is vital to the success of this Program Project. This Mass Spectrometry Core has the physical and intellectual resources needed to support Program Project Investigators in elucidating the role and function of these eicosanoids in health and disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL034300-29
Application #
8644838
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
29
Fiscal Year
2014
Total Cost
$267,031
Indirect Cost
$99,172
Name
New York Medical College
Department
Type
DUNS #
041907486
City
Valhalla
State
NY
Country
United States
Zip Code
10595
Elijovich, Fernando; Milne, Ginger L; Brown, Nancy J et al. (2018) Two Pools of Epoxyeicosatrienoic Acids in Humans: Alterations in Salt-Sensitive Normotensive Subjects. Hypertension 71:346-355
Rocic, Petra; Schwartzman, Michal Laniado (2018) 20-HETE in the regulation of vascular and cardiac function. Pharmacol Ther 192:74-87
Singh, S P; McClung, J A; Bellner, L et al. (2018) CYP-450 Epoxygenase Derived Epoxyeicosatrienoic Acid Contribute To Reversal of Heart Failure in Obesity-Induced Diabetic Cardiomyopathy via PGC-1 ? Activation. Cardiovasc Pharm Open Access 7:
Schragenheim, Joseph; Bellner, Lars; Cao, Jian et al. (2018) EET enhances renal function in obese mice resulting in restoration of HO-1-Mfn1/2 signaling, and decrease in hypertension through inhibition of sodium chloride co-transporter. Prostaglandins Other Lipid Mediat 137:30-39
Soler, Amanda; Hunter, Ian; Joseph, Gregory et al. (2018) Elevated 20-HETE in metabolic syndrome regulates arterial stiffness and systolic hypertension via MMP12 activation. J Mol Cell Cardiol 117:88-99
Wang, Lijun; Zhang, Chengbiao; Su, Xiao-Tong et al. (2017) PGF2?regulates the basolateral K channels in the distal convoluted tubule. Am J Physiol Renal Physiol 313:F254-F261
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
Pandey, Varunkumar; Garcia, Victor; Gilani, Ankit et al. (2017) The Blood Pressure-Lowering Effect of 20-HETE Blockade in Cyp4a14(-/-) Mice Is Associated with Natriuresis. J Pharmacol Exp Ther 363:412-418
Zhang, Bin; Kandhi, Sharath; Yang, Yang-Ming et al. (2017) A novel mechanism of ascorbate direct modulation of soluble epoxide hydrolase. Prostaglandins Other Lipid Mediat 131:59-66
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

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