Influence of Iron Supplementation on DMT1(IRE)-induced Transport of Lead by Brain Barrier Systems in vivo

Objective To investigate the potential involvement of DMT1（IRE） protein in the brain vascular system in vivo during Pb exposure. Methods Three groups of male Sprague-Dawley rats were exposed to Pb in drinking water, among which two groups were concurrently administered by oral gavage once every other day as the low and high Fe treatment group, respectively, for 6 weeks. At the same time, the group only supplied with high Fe was also set as a reference. The animals were decapitated, then brain capillary-rich fraction was isolate from cerebral cortex. Western blot method was used to identify protein expression, and RT-PCR to detect the change of the m RNA. Results Pb exposure significantly increased Pb concentrations in cerebral cortex. Low Fe dose significantly reduced the cortex Pb levels, However, high Fe dose increased the cortex Pb levels. Interestingly, changes of DMT1（IRE） protein in brain capillary-rich fraction were highly related to the Pb level, but those of DMT1（IRE） m RNA were not significantly different. Moreover, the consistent changes in the levels of p-ERK1/2 or IRP1 with the changes in the levels of DMT1（IRE）. Conclusion These results suggest that Pb is transported into the brain through DMT1（IRE）, and the ERK MAPK pathway is involved in DMT1（IRE）-mediated transport regulation in brain vascular system in vivo.

Sodium glutamate and gamma-aminobutyric acid affect iron metabolism in the rat caudate putamen

Glutamic acid and gamma-aminobutyric acid （GABA） influence iron content in the substantia nigra and globus pallidus, although the mechanisms of action remain unclear. The present study measured iron content and changes in divalent metal transporter 1 （DMT1） and hephaestin expression in the substantia nigra and caudate putamen, and explored the effects of GABA and glutamic acid on iron metabolism. Results demonstrated that iron content and DMT1 non iron response element [DMT1 （-IRE）] expression were significantly greater but hephaestin expression was significantly lower in the caudate putamen of the monosodium glutamate group compared with the control group. No significant difference in iron content was detected between the GABA and control groups. DMT1 （-IRE） expression was significantly reduced, but hephaestin expressiori was significantly increased in the GABA group compared with the control group. In addition, there was no significant difference in tyrosine hydroxylase expression between monosodium glutamate and GABA groups and the control group. These results suggested that glutamate affected iron metabolism in the caudate putamen by increasing DMTI（-IRE） and decreasing hephaestin expression. In addition, GABA decreased DMT1 （-IRE） expression in the caudate putamen.