Down-regulation of GTP cyclohydrolase I and tetrahydrobiopterin by melatonin.
Tetrahydrobiopterin (BH4) is spontaneously released and extracellularly exerts a toxic effect preferentially on catecholamine cells. Its synthesis rate is mainly determined by the activity of the enzyme GTP cyclohydrolase I (GTPCH). In the present study, role of melatonin BH4 synthesis was determined using the catecholaminergic CATH.a cells. The neurohormone dose-dependently reduced both intracellular and extracellular BH4 levels. This was due to both direct inhibition of catalytic activity of the existing GTPCH enzyme and down-regulation of GTPCH gene expression. Thus, melatonin is an effective down-regulator of BH4 synthesis and is a potential therapeutic agent with which to control BH4 level in aberrant conditions where it may rise to a toxic level.
Jang
Y J
YJ
Department of Biochemistry, University of Ulsan College of Medicine, Seoul, Korea.
Hong
H N
HN
Lee
J D
JD
Hwang
O
O
D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000096:biosynthesis; D001921:Brain; D002460:Cell Line; D006136:GTP Cyclohydrolase / Q000235:genetics* / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007700:Kinetics; D008550:Melatonin / Q000494:pharmacology*; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects*
D001708:Biopterins; D006136:GTP Cyclohydrolase; C003402:sapropterin; D008550:Melatonin