title: Effect of peripherally administered lipopolysaccharide (LPS) on GTP cyclohydrolase I, tetrahydrobiopterin and norepinephrine in the locus coeruleus in mice.
abstract: Lipopolysaccharide (LPS), an endotoxin released from the outer membranes of Gram-negative bacteria, triggers cells to synthesize and release inflammatory cytokines that may progress to septic shock in vivo. We found that LPS enhances tetrahydrobiopterin (BH4) biosynthesis by inducing the biosynthetic enzyme GTP cyclohydrolase I (GCH) in vitro in the mouse neuroblastoma cell line N1E-115. Furthermore, we observed that gene expression of GCH in the locus coeruleus (LC) in mice was enhanced by peripheral administration of LPS, resulting in increased concentrations of BH4, and norepinephrine, and its metabolite 4-hydroxy-3-methoxyphenylglycol (MHPG). These results suggest that tyrosine hydroxylase (TH) activity is increased by increased content of BH4 due to enhanced mRNA expression of GCH in the LC resulting in the increase in norepinephrine in the LC during endotoxemia. LPS in blood may act as a stressor to increase norepinephrine biosynthesis in the mouse LC.
authors.affiliation: Department of Physiology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ota
authors.forename: Y S
authors.initials: YS
authors.lastname: Kaneko
authors.forename: K
authors.initials: K
authors.lastname: Mori
authors.forename: A
authors.initials: A
authors.lastname: Nakashima
authors.forename: I
authors.initials: I
authors.lastname: Nagatsu
authors.forename: T
authors.initials: T
authors.lastname: Nagatsu
mesh_terms: D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000096:biosynthesis; D045744:Cell Line, Tumor; D006136:GTP Cyclohydrolase / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism*; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D051379:Mice; D009638:Norepinephrine / Q000096:biosynthesis*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D001708:Biopterins; D008734:Methoxyhydroxyphenylglycol; D014446:Tyrosine 3-Monooxygenase; D006136:GTP Cyclohydrolase; C003402:sapropterin; D009638:Norepinephrine