Chun Y S, Choi E, Kim G T, Lee M J, Lee M J, Lee S E, Kim M S, Park J W
Department of Pharmacology and Heart Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-799, Korea.
Biochem Biophys Res Commun. 2000 Feb 16;268(2):652-6. doi: 10.1006/bbrc.2000.2180.
The replacement of heme iron by cobalt or nickel in a putative oxygen sensor is supposed to reduce oxygen binding to the heme protein, resulting in HIF-1 activation and erythropoietin (EPO) induction. According to this hypothesis, zinc might be another example of a transition metal which is capable of stimulating EPO production. By substituting for heme iron, zinc protoporphyrin IX is produced, which has a known low oxygen affinity. However, it has been reported that zinc fails to induce EPO in normoxia, and that it suppresses EPO production in hypoxic cells. This unexpected effect of zinc on EPO production is not understood. In this study, we found that zinc induced the accumulation and nuclear translocation of hypoxia-inducible factor (HIF)-1alpha but inhibited the nuclear translocation of HIF-1beta, which inactivated HIF-1 and suppressed EPO mRNA induction in hypoxic cells.
在假定的氧传感器中，用钴或镍替代血红素铁被认为会减少氧与血红素蛋白的结合，从而导致低氧诱导因子-1（HIF-1）激活和促红细胞生成素（EPO）诱导。根据这一假说，锌可能是另一个能够刺激EPO产生的过渡金属实例。通过替代血红素铁，可生成具有已知低氧亲和力的锌原卟啉IX。然而，据报道，锌在常氧条件下无法诱导EPO产生，并且它会抑制低氧细胞中EPO的产生。锌对EPO产生的这种意外作用尚不清楚。在本研究中，我们发现锌诱导了低氧诱导因子（HIF）-1α的积累和核转位，但抑制了HIF-1β的核转位，这使HIF-1失活并抑制了低氧细胞中EPO mRNA的诱导。
