抄録
Hypoxia causes a variety of adaptive responses through hypoxia-inducible factor-1α (HIF-1α), activation of which induces not only red blood cell production and vessel growth but also anaerobic metabolism through the increase in glucose transporter isoforms and glycolytic enzymes. Interestingly, it has recently been reported that HIF-1α expression could be induced even in normoxia by some essential trace elements such as vanadium (V) and cobalt (Co). Oral administration of each element to diabetic rats caused a significant decrease in blood glucose. Particularly, V normalized the blood glucose. V was expected as one of the candidates of antidiabetic agent, whereas the mechanism(s) for V-induced HIF-1α expression is poorly understood. In this study, we compared the effect of V on HIF-1α expression with that of Co in detail since there were only a few reports on V-induced HIF-1α expression. When 293 cells were treated by V or Co with different exposure time, 100 mM V transiently induced HIF-1α expression within 6∼12 hr after the treatment, in contrast to the persistent activation by Co (100 mM) up to 24 hr. Although it was pointed out that H2O2 mediated HIF -1α activation due to V as well as Co, treatment of 0.4 mM H2O2 for 1 hr did not cause the activation. The results suggest that a new explanation is required with regard to V-induced HIF-1α activation. In order to characterize the pathway in detail, we plan to use some HIF-1α-specific inhibitors. [Jpn J Physiol 55 Suppl:S228 (2005)]
