Ph.D. Program in Nutrition and Food Science, Fu-Jen Catholic University, Hsinchuang, New Taipei City, Taiwan.
J Inorg Biochem. 2013 Nov;128:221-8. doi: 10.1016/j.jinorgbio.2013.07.026. Epub 2013 Jul 22.
Aluminum (Al) overload is correlated with hypochromic anemia. It is possible that Al impedes heme biosynthesis and degradation by affecting the activity of biosynthetic enzymes. However, the molecular mechanisms by which Al affects these enzymes are unknown. Here, we show that long-term exposure of Sprague-Dawley rats to Al decreased hemoglobin concentration and the hematocrit level. In addition, the activity of aminolevulinic acid dehydratase (ALA-D) in rat liver was reduced, but heme oxygenase (HO) activity was enhanced, suggesting an impairment of heme homeostasis. The increase in HO activity was due to up-regulation of mRNA and protein of an inducible HO isozyme, HO-1. Furthermore, we found that reactive oxygen species (ROS)-mediated activation of c-Jun N-terminal kinase (JNK) was critical for HO-1 induction by Al, because ROS scavengers and JNK inhibitors abrogated enhancement of HO-1 by Al in rat hepatocytes. Thus, Al enhances HO-1 expression through the ROS-JNK pathway, which may enhance HO activity and accelerate degradation of heme, leading to hypochromic anemia.
铝（Al）过载与低色素性贫血相关。铝可能通过影响生物合成酶的活性来阻碍血红素的生物合成和降解。然而，铝影响这些酶的分子机制尚不清楚。在这里，我们表明，长期暴露于铝的 Sprague-Dawley 大鼠血红蛋白浓度和血细胞比容水平降低。此外，大鼠肝脏中氨基酮戊酸脱水酶（ALA-D）的活性降低，而血红素加氧酶（HO）的活性增强，表明血红素稳态受到损害。HO 活性的增加是由于诱导型 HO 同工酶 HO-1 的 mRNA 和蛋白表达上调所致。此外，我们发现活性氧（ROS）介导的 c-Jun N 端激酶（JNK）的激活对于铝诱导 HO-1 至关重要，因为 ROS 清除剂和 JNK 抑制剂消除了铝在大鼠肝细胞中增强 HO-1 的作用。因此，铝通过 ROS-JNK 途径增强 HO-1 的表达，这可能增强 HO 活性并加速血红素的降解，导致低色素性贫血。
