Pea Ferritin Stability under Gastric pH Conditions Determines the Mechanism of Iron Uptake in Caco-2 Cells.
Pea Ferritin Stability under Gastric pH Conditions Determines the Mechanism of Iron Uptake in Caco-2 Cells.
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DOI：
10.1093/jn/nxy096
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发表时间：
2018-08-01
期刊：
影响因子：
--
通讯作者：
Fairweather-Tait S
中科院分区：
文献类型：
--
作者：
Perfecto A;Rodriguez-Ramiro I;Rodriguez-Celma J;Sharp P;Balk J;Fairweather-Tait S
缺铁是一个持久的全球健康问题，需要新的治疗方法。大豆来源的铁蛋白（一种分子量为550 kDa的铁储存蛋白）的铁吸收与生物可利用的硫酸亚铁（FeSO 4）相当。然而，据报道，铁蛋白的吸收涉及内吞机制，独立于二价金属离子转运蛋白1（DMT-1），非血红素铁的转运蛋白。我们的总体目标是研究从豌豆（豌豆）作为食品补充剂的纯化铁蛋白的潜力，通过测量其在胃pH值处理下的稳定性和铁摄取到Caco-2细胞的机制。Caco-2细胞用天然或胃pH处理的豌豆铁蛋白与非血红素铁摄取的饮食调节剂、靶向DMT-1的小干扰RNA或内吞作用的化学抑制剂组合处理。细胞铁蛋白的形成，铁吸收的替代措施，和使用特异性抗体的豌豆铁蛋白的内化进行了测量。还比较了等摩尔浓度的天然豌豆铁蛋白和FeSO 4对活性氧（ROS）产生的影响。豌豆铁蛋白暴露于胃pH处理被降解，释放的铁被DMT-1转运到Caco-2细胞中。DMT-1和非血红素铁吸收的抑制剂使铁吸收减少26- 40%。相反，在胃pH值治疗的情况下，天然豌豆铁蛋白的铁吸收不受非血红素铁吸收抑制剂的影响，并且观察到该蛋白质在Caco-2细胞中被内化。氯丙嗪（网格蛋白介导的内吞作用抑制剂）减少了约30%的细胞内的天然豌豆铁蛋白含量，这证实了天然豌豆铁蛋白通过网格蛋白介导的内吞途径转运到细胞中。此外，与FeSO 4相比，天然豌豆铁蛋白产生的ROS减少了60%。考虑到非血红素膳食抑制剂对铁的吸收没有影响，并且相对于FeSO 4的氧化电位较低，完整的豌豆铁蛋白似乎是一种有前途的铁补充剂。
Iron deficiency is an enduring global health problem that requires new remedial approaches. Iron absorption from soybean-derived ferritin, an ∼550-kDa iron storage protein, is comparable to bioavailable ferrous sulfate (FeSO4). However, the absorption of ferritin is reported to involve an endocytic mechanism, independent of divalent metal ion transporter 1 (DMT-1), the transporter for nonheme iron. Our overall aim was to examine the potential of purified ferritin from peas (Pisum sativum) as a food supplement by measuring its stability under gastric pH treatment and the mechanisms of iron uptake into Caco-2 cells. Caco-2 cells were treated with native or gastric pH–treated pea ferritin in combination with dietary modulators of nonheme iron uptake, small interfering RNA targeting DMT-1, or chemical inhibitors of endocytosis. Cellular ferritin formation, a surrogate measure of iron uptake, and internalization of pea ferritin with the use of specific antibodies were measured. The production of reactive oxygen species (ROS) in response to equimolar concentrations of native pea ferritin and FeSO4 was also compared. Pea ferritin exposed to gastric pH treatment was degraded, and the released iron was transported into Caco-2 cells by DMT-1. Inhibitors of DMT-1 and nonheme iron absorption reduced iron uptake by 26–40%. Conversely, in the absence of gastric pH treatment, the iron uptake of native pea ferritin was unaffected by inhibitors of nonheme iron absorption, and the protein was observed to be internalized in Caco-2 cells. Chlorpromazine (clathrin-mediated endocytosis inhibitor) reduced the native pea ferritin content within cells by ∼30%, which confirmed that the native pea ferritin was transported into cells via a clathrin-mediated endocytic pathway. In addition, 60% less ROS production resulted from native pea ferritin in comparison to FeSO4. With consideration that nonheme dietary inhibitors display no effect on iron uptake and the low oxidative potential relative to FeSO4, intact pea ferritin appears to be a promising iron supplement.
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影响因子：
3.7
作者：
Pereira DI;Mergler BI;Faria N;Bruggraber SF;Aslam MF;Poots LK;Prassmayer L;Lönnerdal B;Brown AP;Powell JJ
通讯作者：
Powell JJ
影响因子：
4.8
作者：
Li, Chaorui;Fu, Xiaoping;Zhao, Guanghua
通讯作者：
Zhao, Guanghua
影响因子：
4.2
作者：
Martin, Carol D. San;Garri, Carolina;Nunez, Marco T.
通讯作者：
Nunez, Marco T.
影响因子：
4.3
作者：
Bejjani, Satyanarayana;Pullakhandam, Raghu;Nair, K. Madhavan
通讯作者：
Nair, K. Madhavan
DOI：
10.1016/0304-4165(80)90028-8
发表时间：
1980-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
BIENFAIT, HF;VANDENBRIEL, ML
通讯作者：
VANDENBRIEL, ML