This project is aimed at understanding the biochemical processes by which human leukocytes export the biologically potent lipid mediator, leukotriene (LT) C4. LTC4 is a potent bronchoconstrictor, and has been suggested to be a major contributor to airway constriction. The LTC4 transporter regulates the release of LTC4 and hence potentially regulates the local concentration of this mediator.Plans are to study the biochemical and biophysical properties and the structure function relationship of this protein. To achieve these goals, the investigator proposes to isolate and clone the LTC4 transport protein. A number of specific aims are proposed to achieve this goal and to further investigate the role of LTC4 in the pathogenesis of attenuated pulmonary function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29ES006105-04
Application #
2444219
Study Section
Toxicology Subcommittee 2 (TOX)
Project Start
1994-07-15
Project End
1999-06-30
Budget Start
1997-07-01
Budget End
1998-06-30
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
Lam, Bing K (2003) Leukotriene C(4) synthase. Prostaglandins Leukot Essent Fatty Acids 69:111-6
Lam, Bing K; Austen, K Frank (2002) Leukotriene C4 synthase: a pivotal enzyme in cellular biosynthesis of the cysteinyl leukotrienes. Prostaglandins Other Lipid Mediat 68-69:511-20
Zhao, J L; Austen, K F; Lam, B K (2000) Cell-specific transcription of leukotriene C(4) synthase involves a Kruppel-like transcription factor and Sp1. J Biol Chem 275:8903-10
Lam, B K (1997) Leukotriene C4 synthase: a critical enzyme for the biosynthesis of SRS-A. Front Biosci 2:d380-6
Penrose, J F; Spector, J; Baldasaro, M et al. (1996) Molecular cloning of the gene for human leukotriene C4 synthase. Organization, nucleotide sequence, and chromosomal localization to 5q35. J Biol Chem 271:11356-61