Ke Ya, Chen Yin Yin, Chang Yan Zhong, Duan Xiang Lin, Ho Kwok Ping, Jiang De He, Wang Kui, Qian Zhong Ming
Laboratory of Iron Metabolism, Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Kowloon, Hong Kong.
J Cell Physiol. 2003 Jul;196(1):124-30. doi: 10.1002/jcp.10284.
Non-transferrin-bound iron (NTBI) overtaken by heart cells might be a key cause leading to iron-mediated injury in heart disorders. NTBI uptake by heart cells might be mediated by divalent metal transporter 1 (DMT1). The understanding of the role of DMT1 in heart iron metabolism is fundamental for elucidating the cause resulting in excessive iron in the heart. The study was to evaluate effects of age and dietary iron on DMT1 mRNA expression and protein synthesis in rat heart. DMT1 mRNA expression was determined by RT-PCR and sequence analysis, and DMT1 protein by Western blot analysis. DMT1 mRNAs with or without iron-responsive element (IRE) both were found in rat heart. Expression of two forms of DMT1 mRNAs was the lowest at the age of post-natal day (PND) 7, and then increased with the age, reaching the highest at PND196 (non-IRE form) and PND63 (IRE form), respectively. During different ages, the levels of DMT1 (IRE) mRNA were higher than those of DMT1 (non-IRE) mRNA and were significantly correlated with the non-heme iron contents in the heart. After fed a high iron for 6 weeks, the rats had a sixfold elevation in heart iron and 22% (non-IRE from) and 40% (IRE from) reduction in DMT1 protein compared to the controls. A low iron diet for 6-weeks caused cardiac hypertrophy and heart iron deficiency and also an increase in levels of two forms of DMT1 proteins. However, iron status had no significant effect on DMT1 (IRE) and DMT1 (non-IRE) mRNAs expression in the heart, although it can significantly influence heart transferrin receptor (TfR) mRNA expression. The results demonstrated that DMT1 mRNAs expression in the heart is age-dependent and that two forms of DMT1 mRNAs both are regulated by iron on the post-transcriptional level only.
被心脏细胞摄取的非转铁蛋白结合铁（NTBI）可能是导致心脏疾病中铁介导损伤的关键原因。心脏细胞对NTBI的摄取可能由二价金属转运体1（DMT1）介导。了解DMT1在心脏铁代谢中的作用对于阐明心脏中铁过量的原因至关重要。本研究旨在评估年龄和膳食铁对大鼠心脏中DMT1 mRNA表达和蛋白质合成的影响。通过RT-PCR和序列分析测定DMT1 mRNA表达，通过蛋白质印迹分析测定DMT1蛋白。在大鼠心脏中发现了有或没有铁反应元件（IRE）的DMT1 mRNA。两种形式的DMT1 mRNA表达在出生后第7天（PND）最低，然后随年龄增加，分别在PND196（非IRE形式）和PND63（IRE形式）达到最高。在不同年龄阶段，DMT1（IRE）mRNA水平高于DMT1（非IRE）mRNA水平，且与心脏中非血红素铁含量显著相关。给予高铁饲料6周后，与对照组相比，大鼠心脏铁含量升高6倍，DMT1蛋白减少22%（非IRE形式）和40%（IRE形式）。低铁饮食6周导致心脏肥大和心脏铁缺乏，同时两种形式的DMT1蛋白水平增加。然而，铁状态对心脏中DMT1（IRE）和DMT1（非IRE）mRNA表达没有显著影响，尽管它可以显著影响心脏转铁蛋白受体（TfR）mRNA表达。结果表明，心脏中DMT1 mRNA表达具有年龄依赖性，且两种形式的DMT1 mRNA仅在转录后水平受铁调节。
