A scheme has been developed to isolate and characterize all of the enzymes of tetrahydrobiopterin (BH4) biosynthesis from rat brain. The wide distribution of tetrahydrobiopterin and these enzymes in the brain as well as the lack of effect of specific neurotoxins on some of the enzymes in the pathway suggests that tetrahydrobiopterin and/or these biosynthetic enzymes may have other roles than previously thought. Work is now under way to prepare antibodies to each of these enzymes to use for molecular cloning to obtain DNA probes to investigate the physiological roles.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH001039-07
Application #
3944676
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
1987
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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
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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

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