The Effect Of Estrogen On Iron Metabolsim In Astrocytes And Neurons

Nigral iron accumulation is involved in the etiology of Parkinson’s disease(PD).Recent studies demonstrated that the women are on average 2.1 years older than the men at time of diagnosis. Moreover, medical conditions leading to estrogen depletion(eg,hysterectomy, oophorectomy or short fertile life span) increase the risk of PD. Previous epidemiological studies have demonstrated that the postmenopausal women harbor a higher level of body iron than premenopausal women. There is iron accumulation in bone,liver and spleen in the ovariectomized rats. These indicate estrogen affects iron metabolism in peripheral tissues. The importance of estrogens and iron to physiology and disease has been known for decades, but we often overlook that these two factors interact.Then, what is the role of estrogen on iron metabolism in neurons and astroctyes in midbrain? In the present study, we investigated the effects of estrogen on the iron related proteins in primary cultured astrocytes and neurons. The results were as follows:1. Western blots were applied to detect divalent metal transport 1(DMT1) protein levels. Increased expression of DMT1 was observed in primary cultured astrocytes treated with 17β-estradiol in 10nmol/L group(P < 0.05,compared with the control;n=7).2. Western blots were applied to detect ferroportin1(FPN1) protein levels. Increased expression of FPN1 was observed in primary cultured astrocytes treated with17β-estradiol in both 10nmol/L and 100nmol/L groups(P <0.05, compared with the control compared with 10nmol/L group; n=7). FPN1 expression was further increased in 100nmol/L group compared with 10nmol/L group(P < 0.05).3. Western blots were applied to detect iron regulatory protein 1(IRP1) protein levels.No significant changes of the expression of IRP1 was observed in primary cultured astrocytes treated with 17β-estradiol in both 10nmol/L and 100nmol/L groups(P >0.05; n=8).4. Western blots were applied to detect hypoxia-inducible factor-1α(HIF-1α) protein levels. Increased expression of HIF-1α was observed in primary cultured astrocytes treated with 17β-estradiol in 100nmol/L group(P < 0.05,compared with the control;n=7).5. Western blots were applied to detect hypoxia-inducible factor-2α(HIF-2α) protein levels. No significant changes of the expression of HIF-2α was observed in primary cultured astrocytes treated with 17β-estradiol both 10nmol/L and 100nmol/L groups(P > 0.05; n=5).6. Western blots were applied to detect DMT1 protein levels. Decreased expression of DMT1 was observed in primary cultured VM neurons treated with 17β-estradiol in10nmol/L group(P < 0.05,compared with the control and 100nmol/L group; n=4).7. Western blots were applied to detect FPN1 protein levels. Increased expression of FPN1 was observed in primary cultured VM neurons treated with 17β-estradiol in100nmol/L group(P < 0.05,compared with the control and 100nmol/L group; n=5).8. Decreased expression of IRP1 was observed in primary cultured VM neurons treated with 17β-estradiol in 100nmol/L group(P < 0.05,compared with the control; n=6).9. Western blots were applied to detect HIF-1α protein levels. No significant changes of the expression of HIF-1α was observed in primary cultured VM neurons treated with17β-estradiol in both 10nmol/L and 100nmol/L groups.(P > 0.05; n=6).10. Western blots were applied to detect HIF-2α protein levels. No significant changes of the expression of HIF-2α was observed in primary cultured VM neurons treated with17β-estradiol in both 10nmol/L and 100nmol/L groups.(P > 0.05; n=6).The results suggest that estrogen can increase FPN1 and DMT1 expressions by up-regulating HIF-1α expression in astrocytes. However, estrogen decreased DMT1 and increased FPN1 expressions in neurons by down-regulating IRP1. The study provides an experimental basis for explanation of the gender differences in the incidence of PD, as well as understanding of brain iron metabolism.