title: L-Serine regulates the activities of microglial cells that express very low level of 3-phosphoglycerate dehydrogenase, an enzyme for L-Serine biosynthesis.
abstract: Microglia are well known to become activated during various kinds of neuropathological events. The factors that are responsible for the activation, however, are not fully determined. In the present study, L-Ser was shown to enhance production of nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) by lipopolysaccharide (LPS)-stimulated cultured rat microglial cells. L-Ser, however, did not enhance the expression of mRNAs encoding inducible NO synthase, IL-6 and TNF alpha. On the other hand, astrocytes did not depend on L-Ser for release of IL-6 and TNF alpha. The expression of an enzyme 3-phosphoglycerate dehydrogenase (3PGDH), which is essential for L-Ser biosynthesis from a glycolytic intermediate 3-phosphoglycerate, was investigated. As revealed by Western blotting and immunocytochemical staining, 3PGDH-protein expression in vitro was the highest in astrocytes, intermediate in neurons and the lowest in microglial cells. Semiquantitative RT-PCR showed that microglial cells expressed 3PGDH-mRNA at a lower level than astrocytes. In frozen sections from rat forebrain, only astrocytes were immunoreactive for 3PGDH. The present study suggested that L-Ser is able to modulate microglial function mainly at the translation level because microglial cells cannot synthesize sufficient amount of L-Ser due to the scarce expression of 3PGDH.
authors.affiliation: Department of Physiology, School of Medicine, Ehime University, Shigenobu, Ehime, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sugishita
authors.forename: Y
authors.initials: Y
authors.lastname: Kuwabara
authors.forename: K
authors.initials: K
authors.lastname: Toku
authors.forename: L
authors.initials: L
authors.lastname: Doi
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.forename: J
authors.initials: J
authors.lastname: Mitoma
authors.forename: S
authors.initials: S
authors.lastname: Furuya
authors.forename: Y
authors.initials: Y
authors.lastname: Hirabayashi
authors.forename: N
authors.initials: N
authors.lastname: Maeda
authors.forename: M
authors.initials: M
authors.lastname: Sakanaka
authors.forename: J
authors.initials: J
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects*; D002237:Carbohydrate Dehydrogenases / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D004622:Embryo, Mammalian; D015850:Interleukin-6 / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D050543:Phosphoglycerate Dehydrogenase; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D012694:Serine; D002237:Carbohydrate Dehydrogenases; D050543:Phosphoglycerate Dehydrogenase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat