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

ABSTRACT: Magnesium deficiency is suggested to contribute to many age-related diseases. Hypoxia-inducible factor 1alpha (HIF-1alpha) is known to be a master regulator of hypoxic response. Here we show that hypomagnesemia suppresses reactive oxygen species (ROS)-induced HIF-1alpha 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-1alpha activity was suppressed. This suppression was due to up-regulation of inhibitory PAS (Per/Arnt/Sim) domain protein (IPAS) that was caused by NF-kappaB activation, which resulted from ROS and calcium influx mainly through the T-type calcium channels. Induction of tyrosine hydroxylase, a target of HIF-1,

SUBMITTER: Torii S 

PROVIDER: S-EPMC2707206 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature