Induction of adrenomedullin during hypoxia in cultured human glioblastoma cells

Adrenomedullin is a potent vasodilator peptide originally isolated from phe ochromocytoma. Adrenomedullin is produced by various types of cells includi ng neurons and astrocytes. To explore possible pathophysiological roles of adrenomedullin in hypoxic brain, we studied the effects of hypoxia on the e xpression of adrenomedullin in T98G human glioblastoma cells by radioimmuno assay and northern blot analysis. Expression levels of adrenomedullin mRNA and immunoreactive adrenomedullin levels in the culture medium were increas ed by hypoxia about six- and about threefold, respectively. Treatment with cobalt chloride increased expression levels of adrenomedullin mRNA about th reefold and immunoreactive adrenomedullin levels in the culture medium abou t 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 mai nly by increased transcription. Treatment with cycloheximide caused increas es in adrenomedullin mRNA levels in both normoxic and hypoxic states, raisi ng the possibility that some protein(s) may act as a suppressor of adrenome dullin gene expression in T98G cells. These findings indicate that adrenome dullin is highly induced during hypoxia in T98G glioblastoma cells and sugg est that increased expression of adrenomedullin during hypoxia may be impor tant in the defense against hypoxia or ischemia in the brain.