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

• Published in: Biomedical and environmental sciences Vol. 28; no. 9; pp. 651 - 659
• Main Authors: AN, Dai Zhi, AI, Jun Tao, FANG, Hong Juan, SUN, Ru Bao, SHI, Yun, WANG, Li Li, WANG, Qiang
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.09.2015; Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing 100071, China%Beijing Vocational College of Agriculture, Beijing 102442, China%Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050, China
• Subjects: Animals; Blood-brain barrier; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Cation Transport Proteins - drug effects; Cation Transport Proteins - genetics; Cation Transport Proteins - physiology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Dietary Supplements; Divalent metal transporter 1; Extracellular Signal-Regulated MAP Kinases - metabolism; Gene Expression Regulation - drug effects; Iron; Iron - administration & dosage; Iron - metabolism; Lead; Lead - administration & dosage; Lead - pharmacokinetics; Male; MAP Kinase Signaling System - physiology; MAPK pathway; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; MAPK pathway; Lead; Iron; Blood-brain barrier; Divalent metal transporter 1
• ISSN: 0895-3988; 2214-0190
• DOI: 10.3967/bes2015.091

To investigate the potential involvement of DMT1 (IRE) protein in the brain vascular system in vivo during Pb exposure. 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 mRNA. 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) mRNA 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). 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.