Induction of adrenomedullin during hypoxia in cultured human glioblastoma cells

Tomomi Kitamuro, Kazuhiro Takahashi, Masaharu Nakayama, Osamu Murakami, Wataru Hida, Kunio Shirato, Shigeki Shibahara

研究成果: Article

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Adrenomedullin is a potent vasodilator peptide originally isolated from pheochromocytoma. Adrenomedullin is produced by various types of cells including neurons and astrocytes. To explore possible pathophysiological roles of adrenomedullin in hypoxic brain, we studied the effects of hypoxia on the expression of adrenomedullin in T98G human glioblastoma cells by radioimmunoassay and northern blot analysis. Expression levels of adrenomedullin mRNA and immunoreactive adrenomedullin levels in the culture medium were increased by hypoxia about six- and about threefold, respectively. Treatment with cobalt chloride increased expression levels of adrenomedullin mRNA about threefold and immunoreactive adrenomedullin levels in the culture medium about threefold in T98G cells. Using actinomycin D, we showed that hypoxia did not cause the stabilization of the adrenomedullin mRNA, suggesting that the increased adrenomedullin mRNA levels in response to hypoxia are caused mainly by increased transcription. Treatment with cycloheximide caused increases in adrenomedullin mRNA levels in both normoxic and hypoxic states, raising the possibility that some protein(s) may act as a suppressor of adrenomedullin gene expression in T98G cells. These findings indicate that adrenomedullin is highly induced during hypoxia in T98G glioblastoma cells and suggest that increased expression of adrenomedullin during hypoxia may be important in the defense against hypoxia or ischemia in the brain.

元の言語English
ページ(範囲)1826-1833
ページ数8
ジャーナルJournal of Neurochemistry
75
発行部数5
DOI
出版物ステータスPublished - 2000

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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