L-serine regulates the activities of microglial cells that express very low level of 3-phosphoglycerate dehydrogenase, an enzyme for L-serine biosynthesis

Hiroki Sugishita, Yasuhide Kuwabara, Kazuko Toku, Lisa Doi, Lihua Yang, Junya Mitoma, Shigeki Furuya, Yoshio Hirabayashi, Nobuji Maeda, Masahiro Sakanaka, Junya Tanaka

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

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 α (TNF α) 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 α. On the other hand, astrocytes did not depend on L-Ser for release of IL-6 and TNF α. 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.

Original languageEnglish
Pages (from-to)392-401
Number of pages10
JournalJournal of Neuroscience Research
Volume64
Issue number4
DOIs
Publication statusPublished - May 15 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

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