Abstract

The production of nitric oxide in brain glial cells is stimulated by cytokines and requires the concomitant synthesis of tetrahydrobiopterin. Fibroblasts doubly transfected with tyrosine hydroxylase and GTP cyclohydrolase cDNAs spontaneously produce large amounts of dopamine and have been used in an animal model for Parkinson's disease. A new feedback regulatory protein (GFRP) which interacts with GTP cyclohydrolase has been cloned. The GFRP-GTP cyclohydrolase complex has low activity in the presence of tetrahydrobiopterin and the activity is specifically restored by L-phenylalanine, constituting a new type of metabolic regulation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH001039-28
Application #
2578691
Study Section
Special Emphasis Panel (LNC)
Project Start
Project End
Budget Start
Budget End
Support Year
28
Fiscal Year
1996
Total Cost
Indirect Cost

  Institution

Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Maceyka, Michael; Milstien, Sheldon; Spiegel, Sarah (2007) Shooting the messenger: oxidative stress regulates sphingosine-1-phosphate. Circ Res 100:7-9
Alvarez, Sergio E; Milstien, Sheldon; Spiegel, Sarah (2007) Autocrine and paracrine roles of sphingosine-1-phosphate. Trends Endocrinol Metab 18:300-7
Oskeritzian, Carole A; Milstien, Sheldon; Spiegel, Sarah (2007) Sphingosine-1-phosphate in allergic responses, asthma and anaphylaxis. Pharmacol Ther 115:390-9
Payne, Shawn G; Oskeritzian, Carole A; Griffiths, Rachael et al. (2007) The immunosuppressant drug FTY720 inhibits cytosolic phospholipase A2 independently of sphingosine-1-phosphate receptors. Blood 109:1077-85
Watterson, Kenneth R; Berg, Krystina M; Kapitonov, Dmitri et al. (2007) Sphingosine-1-phosphate and the immunosuppressant, FTY720-phosphate, regulate detrusor muscle tone. FASEB J 21:2818-28
Le Stunff, Herve; Giussani, Paola; Maceyka, Michael et al. (2007) Recycling of sphingosine is regulated by the concerted actions of sphingosine-1-phosphate phosphohydrolase 1 and sphingosine kinase 2. J Biol Chem 282:34372-80
Maceyka, Michael; Milstien, Sheldon; Spiegel, Sarah (2007) Measurement of mammalian sphingosine-1-phosphate phosphohydrolase activity in vitro and in vivo. Methods Enzymol 434:243-56
Mitra, Poulami; Payne, Shawn G; Milstien, Sheldon et al. (2007) A rapid and sensitive method to measure secretion of sphingosine-1-phosphate. Methods Enzymol 434:257-64
Sankala, Heidi M; Hait, Nitai C; Paugh, Steven W et al. (2007) Involvement of sphingosine kinase 2 in p53-independent induction of p21 by the chemotherapeutic drug doxorubicin. Cancer Res 67:10466-74
Spiegel, Sarah; Milstien, Sheldon (2007) Functions of the multifaceted family of sphingosine kinases and some close relatives. J Biol Chem 282:2125-9

Showing the most recent 10 out of 56 publications