RRC ID 45139
著者 Nishimura K, Tokida M, Katsuyama H, Nakagawa H, Matsuo S.
タイトル The effect of hemin-induced oxidative stress on erythropoietin production in HepG2 cells.
ジャーナル Cell Biol Int
Abstract Erythropoietin (EPO) and iron are both indispensable hematopoietic factors and are often studied in humans and rodents. Iron activates prolyl hydroxylases (PHDs) and promotes the degradation of the α-subunit of hypoxia inducible factor (HIF), which regulates EPO production. Iron also causes oxidative stress. Oxidative stress leads to alterations in the levels of multiple factors that regulate HIF and EPO production. It is thought that iron influences EPO production by altering two pathways, namely PHDs activity and oxidative stress. We studied the differential effect of varying concentrations of hemin, an iron-containing porphyrin, on EPO production in HepG2 cells. Hemin at 100 µM reduced EPO mRNA expression. The hemin-induced reduction of EPO mRNA levels was attenuated at concentrations greater than 200 µM and EPO production increased in the presence of 500 µM hemin. In comparison, protoporphyrin IX, iron-free hemin did not influence EPO mRNA expression. Additionally, malondialdehyde (MDA) concentrations and superoxide dismutase (SOD) activity significantly increased with 300 µM hemin. Importantly, the antioxidant tempol inhibited the hemin-induced (500 µM) increase in EPO mRNA levels. In conclusion, these results suggest that restraint of EPO production by hemin was offset by the promotion of EPO production by hemin-induced oxidative stress at hemin concentrations greater than 300 µM.
巻・号 38(11)
ページ 1321-9
公開日 2014-11-1
DOI 10.1002/cbin.10329
PMID 24962609
MeSH Antioxidants / pharmacology Cyclic N-Oxides / pharmacology Erythropoietin / genetics Erythropoietin / metabolism* Hemin / pharmacology* Hep G2 Cells Humans Hypoxia-Inducible Factor 1 / metabolism Malondialdehyde / metabolism Oxidative Stress / drug effects* RNA, Messenger / metabolism Spin Labels Superoxide Dismutase / metabolism Up-Regulation / drug effects
IF 2.571
引用数 5
WOS 分野 CELL BIOLOGY
リソース情報
ヒト・動物細胞 Hep G2 HMV-II(RCB3685)