Ota A, Kaneko Y S, Mori K, Nakashima A, Nagatsu I, Nagatsu T
Department of Physiology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Stress. 2007 Jun;10(2):131-6. doi: 10.1080/10253890701350511.
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.
脂多糖（LPS）是革兰氏阴性菌外膜释放的一种内毒素，可触发细胞合成并释放炎性细胞因子，在体内可能发展为脓毒性休克。我们发现，在小鼠神经母细胞瘤细胞系N1E-115中，LPS在体外通过诱导生物合成酶GTP环化水解酶I（GCH）来增强四氢生物蝶呤（BH4）的生物合成。此外，我们观察到，通过外周给予LPS可增强小鼠蓝斑（LC）中GCH的基因表达，导致BH4、去甲肾上腺素及其代谢物4-羟基-3-甲氧基苯乙二醇（MHPG）的浓度升高。这些结果表明，在内毒素血症期间，由于LC中GCH的mRNA表达增强，BH4含量增加，从而提高了酪氨酸羟化酶（TH）的活性，导致LC中去甲肾上腺素增加。血液中的LPS可能作为一种应激源，增加小鼠LC中去甲肾上腺素的生物合成。
