Inoue Hirofumi, Hanawa Nobuaki, Katsumata Shin-Ichi, Aizawa Yumi, Katsumata-Tsuboi Rie, Tanaka Miori, Takahashi Nobuyuki, Uehara Mariko
Department of Nutritional Science and Food Safety, Faculty of Applied Bioscience, Tokyo University of Agriculture, Japan.
Department of Nutritional Science, Faculty of Applied Bioscience, Tokyo University of Agriculture, Japan.
Heliyon. 2020 Oct 3;6(10):e05059. doi: 10.1016/j.heliyon.2020.e05059. eCollection 2020 Oct.
Iron is an essential trace metal for all biological processes and plays a role in almost every aspect of body growth. Previously, we found that iron-depletion downregulated the expression of proteins, arginine methyltransferase-1 and 3 (PRMT1 and PRMT3), by an iron-specific chelator, deferoxamine (DFO), in rat liver FAO cell line using DNA microarray analysis (unpublished data). However, regulatory mechanisms underlying the association between iron deficiency and PRMT expression are unclear and . In the present study, we revealed that the treatment of cells with two iron-specific chelators, DFO and deferasirox (DFX), downregulated the gene and protein expression of PRMT1 and 3 as compared with the untreated cells. Subsequently, DFO and DFX treatments decreased protein methylation. Importantly, these effects were attenuated by a holo-transferrin treatment. Furthermore, weanling Wistar-strain rats were fed a control diet or an iron-deficient diet for 4 weeks. Dietary iron deficiency was found to decrease the concentration of hemoglobin and liver iron while increasing the heart weight. PRMT and protein methylation levels were also significantly reduced in the iron-deficient group as compared to the control group. To our knowledge, this is the first study to demonstrate that PRMT levels and protein methylation are reduced in iron-deficient models, and .
铁是所有生物过程必需的微量金属，在身体生长的几乎每个方面都发挥作用。此前，我们利用DNA微阵列分析发现，在大鼠肝脏脂肪酸氧化（FAO）细胞系中，铁特异性螯合剂去铁胺（DFO）可使铁耗竭下调蛋白质精氨酸甲基转移酶-1和3（PRMT1和PRMT3）的表达（未发表数据）。然而，铁缺乏与PRMT表达之间关联的调控机制尚不清楚。在本研究中，我们发现，与未处理细胞相比，用两种铁特异性螯合剂DFO和地拉罗司（DFX）处理细胞可下调PRMT1和3的基因及蛋白质表达。随后，DFO和DFX处理降低了蛋白质甲基化水平。重要的是，全转铁蛋白处理可减弱这些作用。此外，将断乳的Wistar品系大鼠喂以对照饮食或缺铁饮食4周。发现饮食缺铁会降低血红蛋白浓度和肝脏铁含量，同时增加心脏重量。与对照组相比，缺铁组的PRMT和蛋白质甲基化水平也显著降低。据我们所知，这是第一项证明在缺铁模型中PRMT水平和蛋白质甲基化降低的研究。
