2009年7月
Magnesium Deficiency Causes Loss of Response to Intermittent Hypoxia in Paraganglion Cells
JOURNAL OF BIOLOGICAL CHEMISTRY
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- 巻
- 284
- 号
- 28
- 開始ページ
- 19077
- 終了ページ
- 19089
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1074/jbc.M109.004424
- 出版者・発行元
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Magnesium deficiency is suggested to contribute to many age-related diseases. Hypoxia-inducible factor 1 alpha (HIF-1 alpha) is known to be a master regulator of hypoxic response. Here we show that hypomagnesemia suppresses reactive oxygen species (ROS)-induced HIF-1 alpha 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 (CoCl(2)) or exposed to intermittent hypoxia, ROS-mediated HIF-1 alpha activity was suppressed. This suppression was due to up-regulation of inhibitory PAS (Per/Arnt/Sim) domain protein (IPAS) that was caused by NF-kappa B 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 CoCl(2) 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, CoCl(2) 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.
- リンク情報
- ID情報
-
- DOI : 10.1074/jbc.M109.004424
- ISSN : 0021-9258
- PubMed ID : 19433582
- Web of Science ID : WOS:000267711500056