Hypoxic upregulation of tyrosine hydroxylase gene expression is paralleled, but not induced, by increased generation of reactive oxygen species in PC12 cells

Oxygen sensing was investigated in rat pheochromocytoma PC12 cells. They re spond to hypoxia with an increased intracellular generation of reactive oxy gen species (ROS), measured by oxidation of dihydrorhodamine 123, This incr ease is abolished by intracellular superoxide scavenging by Mn(III)tetrakis (1-methyl-4-pyridyl)-porphyrin, and reduced or absent in the presence of th e flavoprotein/complex I inhibitors, diphenyleneiodonium and rotenone, The same inhibitors, but neither intra- nor extracellular (superoxide dismutase ) superoxide scavenging, abolish the hypoxia-induced increase in tyrosine h ydroxylase (TH) gene expression. Thus, ROS production increases in PC12 cel ls during hypoxia, but this is not the cause of hypoxic TH mRNA upregulatio n that involves a flavoprotein, (C) 1999 Federation of European Biochemical Societies.