Abstract

A range of halogenated alkenes are selective nephrotoxins, and some are nephrocarcinogenic, in rodent species. The bioactivation mechanism of haloalkenes includes hepatic glutathione S-conjugate formation, hydrolysis of the glutathione S-conjugates to the corresponding cysteine S-conjugates, transport of the cysteine S-conjugates to the kidney, and bioactivatioan by renal cysteine conjugate b-lyase. Most haloaklene-derived cystein S-conjugates are nephrotoxic in vivo and cytotoxic in vitro. In addition, chloroalkene- and bromine-containing, fluoroalkene-derived conjugates are mutagenic. The objective of our studies is to elucidate the detailed reaction mechanisms involved at the several steps in the pathway. Massspectrometry is used to help characterize conjugates and metabolites prepared by synthesis or derived from metabolism studies. Hence, the UCSF Mass Spectrometry Facility will help us in attaining our research goals by assisting in the elucidation of structures of conjugates and metabolites.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001614-17
Application #
6281146
Study Section
Project Start
1998-03-01
Project End
1999-02-28
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
17
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

MacRae, Andrew J; Mayerle, Megan; Hrabeta-Robinson, Eva et al. (2018) Prp8 positioning of U5 snRNA is linked to 5' splice site recognition. RNA 24:769-777
Katsuno, Yoko; Qin, Jian; Oses-Prieto, Juan et al. (2018) Arginine methylation of SMAD7 by PRMT1 in TGF-?-induced epithelial-mesenchymal transition and epithelial stem-cell generation. J Biol Chem 293:13059-13072
Sahoo, Pabitra K; Smith, Deanna S; Perrone-Bizzozero, Nora et al. (2018) Axonal mRNA transport and translation at a glance. J Cell Sci 131:
Tran, Vy M; Wade, Anna; McKinney, Andrew et al. (2017) Heparan Sulfate Glycosaminoglycans in Glioblastoma Promote Tumor Invasion. Mol Cancer Res 15:1623-1633
Liu, Tzu-Yu; Huang, Hector H; Wheeler, Diamond et al. (2017) Time-Resolved Proteomics Extends Ribosome Profiling-Based Measurements of Protein Synthesis Dynamics. Cell Syst 4:636-644.e9
Bikle, Daniel D (2016) Extraskeletal actions of vitamin D. Ann N Y Acad Sci 1376:29-52
Twiss, Jeffery L; Fainzilber, Mike (2016) Neuroproteomics: How Many Angels can be Identified in an Extract from the Head of a Pin? Mol Cell Proteomics 15:341-3
Cil, Onur; Phuan, Puay-Wah; Lee, Sujin et al. (2016) CFTR activator increases intestinal fluid secretion and normalizes stool output in a mouse model of constipation. Cell Mol Gastroenterol Hepatol 2:317-327
Posch, Christian; Sanlorenzo, Martina; Vujic, Igor et al. (2016) Phosphoproteomic Analyses of NRAS(G12) and NRAS(Q61) Mutant Melanocytes Reveal Increased CK2? Kinase Levels in NRAS(Q61) Mutant Cells. J Invest Dermatol 136:2041-2048
Julien, Olivier; Zhuang, Min; Wiita, Arun P et al. (2016) Quantitative MS-based enzymology of caspases reveals distinct protein substrate specificities, hierarchies, and cellular roles. Proc Natl Acad Sci U S A 113:E2001-10

Showing the most recent 10 out of 630 publications