Chemical hypoxia-induced stimulation of polyamine biosynthesis and ornithine decarboxylase gene transcription in C6 glioma cells

Abstract

Mari Itoh, Naoyoshi Nishibori, Song Her, Mi-Sook Lee, Kyoji Morita

Background: Polyamines, aliphatic polycationic compounds distributed ubiquitously in the living organisms, are considered to be implicated in various cellular processes, and furthermore speculated to play a possible pathophysiological role in physical and mental disorders. In particular, the regulation of polyamine metabolism in damaged glial cells seems interesting and important to understand a possible connection of polyamines with the brain functions. On the other hand, previous studies have shown that ornithine decarboxylase (ODC), the enzyme catalyzing the rate-limiting step of polyamine biosynthesis, can be activated during the period of recovery from various damage in the brain, but little is known about the effects of toxic insults on the expression of ODC gene in neuronal and glial cells. Aim: Based on the hypothesis that noxious impacts on the brain might be able to increase polyamine production in glial cells, thereby protecting the neuronal cell functions against toxic injuries, the effects of chemical hypoxia on polyamine production and ODC gene transcription were investigated in C6 glioma cells as an in vitro model system. Methods: The cellular contents of polyamines were determined by a HPLC assay, and ODC gene transcription was analyzed by measuring its mRNA levels by a one-step RT-PCR method. Results: In consequence, both cobalt and azide were shown to increase the cellular polyamine contents through elevating ODC mRNA levels under the conditions in which hypoxia-inducible factor-1α (Hif-1α) gene was expressed. Conclusion: Therefore, chemical hypoxia is speculated to induce ODC gene transcription, thus resulting in the increment of polyamine contents in glial cells, thereby contributing to the recovery of brain function from hypoxic injury.

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