The Role of Ferric Nitrilotriacetate in Renal Carcinogenesis and Cell Death: From Animal Models to Clinical Implications.
The Role of Ferric Nitrilotriacetate in Renal Carcinogenesis and Cell Death: From Animal Models to Clinical Implications.
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DOI：
10.3390/cancers14061495
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发表时间：
2022-03-15
期刊：
影响因子：
5.2
通讯作者：
Okazaki Y
中科院分区：
文献类型：
--
作者：
Okazaki Y
铁对于细胞生长和生存至关重要。因此，铁缺乏会对机体产生多效性影响，而铁超载也会通过氧化组织损伤而产生有害影响，从而导致人类肝硬化、糖尿病和心肌病。非血红素铁包含三价铁离子 (Fe(III))，其在转铁蛋白、铁蛋白或不稳定铁库中比亚铁离子 (Fe(II)) 更为突出；相反，亚铁离子比三价铁离子产生更多的活性氧（ROS）。在啮齿类动物中，次氮基三乙酸铁 (Fe-NTA) 通过谷胱甘肽循环依赖性铁还原引发肝和肾氧化脂质，最终导致肾细胞癌 (RCC)。除了铁介导的致癌作用之外，铁依赖性脂质过氧化积累至致死水平还会引发铁死亡。在此，讨论了铁和 ROS 介导的肾细胞癌的机制以及铁死亡的治疗可能性。铁对于细胞生长至关重要，各种铁蛋白和含血红素蛋白参与多种细胞功能，例如 DNA 合成、氧运输和催化反应。因此，铁缺乏会引起多效性效应，例如低色素性小细胞性贫血和生长障碍，而铁超载也会因氧化损伤而有害。为了防止铁介导的活性氧 (ROS) 的产生，合成铁蛋白以在细胞中储存过量的铁，这与血清铁蛋白浓度监测铁螯合治疗效果的临床用途一致。在探索铁诱导的氧化应激的动物模型中，次氮基三乙酸铁 (Fe-NTA) 在重复腹腔注射 Fe-NTA 后被证明可引发肝肾脂质过氧化和肾细胞癌 (RCC) 的发展。在此，结合对人类RCC发病机制与铁代谢关系的总结，对目前对谷胱甘肽循环依赖性铁还原介导的Fe-NTA诱导的氧化应激以及肾癌发生的分子机制的认识进行总结。除了铁介导的致癌作用之外，还讨论了由铁依赖性脂质过氧化积累引发并与致癌作用有关的铁死亡。
Iron is essential for cellular growth and survival. As a consequence, iron deficiency causes pleiotropic effects on the organism, while iron overload is also deleterious by means of oxidative tissue injury, which causes hepatic cirrhosis, diabetes mellitus, and cardiomyopathy in humans. Non-heme iron comprises ferric ion (Fe(III)), which is much more prominent in the transferrin, ferritin, or labile iron pool than the ferrous ion (Fe(II)); in contrast, ferrous ion yields more reactive oxygen species (ROS) than ferric ion does. In rodents, ferric nitrilotriacetate (Fe-NTA) elicits hepatic and renal oxidized lipids via a glutathione-cycle-dependent iron reduction that eventually causes renal cell carcinoma (RCC). In addition to iron-mediated carcinogenesis, ferroptosis is triggered by the iron-dependent accumulation of lipid peroxidation to lethal levels. Here, the mechanisms of iron- and ROS-mediated RCC and the therapeutic possibility of ferroptosis are discussed. Iron is essential for cellular growth, and various ferroproteins and heme-containing proteins are involved in a myriad of cellular functions, such as DNA synthesis, oxygen transport, and catalytic reactions. As a consequence, iron deficiency causes pleiotropic effects, such as hypochromic microcytic anemia and growth disturbance, while iron overload is also deleterious by oxidative injury. To prevent the generation of iron-mediated reactive oxygen species (ROS), ferritin is synthesized to store excess iron in cells that are consistent with the clinical utility of the serum ferritin concentration to monitor the therapeutic effect of iron-chelation. Among the animal models exploring iron-induced oxidative stress, ferric nitrilotriacetate (Fe-NTA) was shown to initiate hepatic and renal lipid peroxidation and the development of renal cell carcinoma (RCC) after repeated intraperitoneal injections of Fe-NTA. Here, current understanding of Fe-NTA-induced oxidative stress mediated by glutathione-cycle-dependent iron reduction and the molecular mechanisms of renal carcinogenesis are summarized in combination with a summary of the relationship between the pathogenesis of human RCC and iron metabolism. In addition to iron-mediated carcinogenesis, the ferroptosis that is triggered by the iron-dependent accumulation of lipid peroxidation and is implicated in the carcinogenesis is discussed.
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影响因子：
5.7
作者：
Cheng Z;Akatsuka S;Li GH;Mori K;Takahashi T;Toyokuni S
通讯作者：
Toyokuni S
小鼠肾细胞癌建模：Bap1 和 Pbrm1 失活驱动肿瘤分级。
影响因子：
28.2
作者：
Gu YF;Cohn S;Christie A;McKenzie T;Wolff N;Do QN;Madhuranthakam AJ;Pedrosa I;Wang T;Dey A;Busslinger M;Xie XJ;Hammer RE;McKay RM;Kapur P;Brugarolas J
通讯作者：
Brugarolas J
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
DOI：
10.1111/j.1349-7006.1995.tb03022.x
发表时间：
1995-11-01
期刊：
JAPANESE JOURNAL OF CANCER RESEARCH
影响因子：
--
作者：
DEGUCHI, J;MIYAMOTO, M;OKADA, S
通讯作者：
OKADA, S
影响因子：
3.5
作者：
Deiana, M;Aruoma, OI;Dessi, MA
通讯作者：
Dessi, MA