Magnesium deficiency causes loss of response to intermittent hypoxia in paraganglion cells

Satoru Torii, Kentaro Kobayashi, Masayuki Takahashi, Kasumi Katahira, Kenji Goryo, Natsuki Matsushita, Ken Ichi Yasumoto, Yoshiaki Fujii-Kuriyama, Kazuhiro Sogawa

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


Magnesium deficiency is suggested to contribute to many age-related diseases. Hypoxia-inducible factor 1α (HIF-1α) is known to be a master regulator of hypoxic response. Here we show that hypomagnesemia suppresses reactive oxygen species (ROS)-induced HIF-1α activity in paraganglion cells of the adrenal medulla and carotid body. In PC12 cells cultured in the low magnesium medium and treated with cobalt chloride (CoCl2) or exposed to intermittent hypoxia, ROS-mediated HIF-1α activity was suppressed. This suppression was due to up-regulation of inhibitory PAS (Per/Arnt /Sim) domain protein (IPAS) that was caused by NF-ΚB activation, which resulted from ROS and calcium influx mainly through the T-type calcium channels. Induction of tyrosine hydroxylase, a target of HIF-1, by CoCl2 injection was suppressed in the adrenal medulla of magnesium-deficient mice because of up-regulation of IPAS. Also in the carotid body of magnesium-deficient mice, CoCl2 and chronic intermittent hypoxia failed to enhance the tyrosine hydroxylase expression. These results demonstrate that serum magnesium levels are a key determinant for ROS-induced hypoxic responses.

Original languageEnglish
Pages (from-to)19077-19089
Number of pages13
JournalJournal of Biological Chemistry
Issue number28
Publication statusPublished - 2009 Jul 10

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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