细胞铁死亡发生与调控机制的研究进展
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摘要
<正>细胞死亡无论在生理还是在病理条件下都是无法避免的重要环节。传统意义上细胞死亡主要分为凋亡(apoptosis)和坏死(necrosis)两大主要类型,但近年来却发现在诸多病理生理情况下亦有自噬(autophagy)、胀亡(oncosis)、副凋亡(paraptosis)、焦亡(pyroptosis)等多种方式参与其中。越来越多细胞死亡方式的发现为进一步明确疾病的发生机制以及为
With the development of modern medical research,it has been found that there are many forms of cell death under lots of physiological or pathological conditions. Among them,necrosis and apoptosis are the 2 main forms of cell death. In recent years,varieties of new cell death patterns,such as autophagy,oncosis and paraptosis,have been discovered. In 2012,Dixon et al first discovered and reported a new form of iron-dependent cell death,ferroptosis. In this review,we try to expound the morphological and biochemical features of ferroptosis and its related diseases in detail,so as to deepen our understanding of cell death,thus providing new ideas for the prevention and treatment of clinically relevant diseases.
With the development of modern medical research,it has been found that there are many forms of cell death under lots of physiological or pathological conditions. Among them,necrosis and apoptosis are the 2 main forms of cell death. In recent years,varieties of new cell death patterns,such as autophagy,oncosis and paraptosis,have been discovered. In 2012,Dixon et al first discovered and reported a new form of iron-dependent cell death,ferroptosis. In this review,we try to expound the morphological and biochemical features of ferroptosis and its related diseases in detail,so as to deepen our understanding of cell death,thus providing new ideas for the prevention and treatment of clinically relevant diseases.
引文
[1]Dixon SJ,Lemberg KM,Lamprecht MR,et al.Ferroptosis:an iron-dependent form of nonapoptotic cell death[J].Cell,2012,149(5):1060-1072.
[2]Dolma S,Lessnick SL,Hahn WC,et al.Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells[J].Cancer Cell,2003,3(3):285-296.
[3]Yang WS,Stockwell BR.Synthetic lethal screening identifies compounds activating iron-dependent,nonapoptotic cell death in oncogenic-RAS-harboring cancer cells[J].Chem Biol,2008,15(3):234-245.
[4]Yang WS,Stockwell BR.Ferroptosis:death by lipid peroxidation[J].Trends Cell Biol,2016,26(3):165-176.
[5]Friedmann Angeli JP,Schneider M,Proneth B,et al.Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice[J].Nat Cell Biol,2014,16(12):1180-1191.
[6]周彩虹,黄启福.凋亡与肿瘤及其治疗进展[J].中国病理生理杂志,2004,20(11):2124-2133.
[7]洪远,郭松雪,张建民.自噬在创伤性脑损伤中的作用[J].中国病理生理杂志,2011,27(8):1652-1656.
[8]Galluzzi L,Vitale I,Abrams JM,et al.Molecular definitions of cell death subroutines:recommendations of the Nomenclature Committee on Cell Death 2012[J].Cell Death Differ,2012,19(1):107-120.
[9]安鹏.铁代谢稳态失衡Hepcidin调控机制研究[D].上海:华东理工大学,2014.
[10]Bogdan AR,Miyazawa M,Hashimoto K,et al.Regulators of iron homeostasis:new players in metabolism,cell death,and disease[J].Trends Biochem Sci,2016,41(3):274-286.
[11]Tejedor JR,Papasaikas P,Valcarcel J.Genome-wide identification of Fas/CD95 alternative splicing regulators reveals links with iron homeostasis[J].Mol Cell,2015,57(1):23-38.
[12]Xie Y,Hou W,Song X,et al.Ferroptosis:process and function[J].Cell Death Differ,2016,23(3):369-379.
[13]Louandre C,Marcq I,Bouhlal H,et al.The retinoblastoma(Rb)protein regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma cells[J].Cancer Lett,2015,356(2 Pt B):971-977.
[14]Sun X,Ou Z,Chen R,et al.Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells[J].Hepatology,2016,63(1):173-184.
[15]Lorincz T,Jemnitz K,Kardon T,et al.Ferroptosis is involved in acetaminophen induced cell death[J].Pathol Oncol Res,2015,21(4):1115-1121.
[16]Eling N,Reuter L,Hazin J,et al.Identification of artesunate as a specific activator of ferroptosis in pancreatic cancer cells[J].Oncoscience,2015,2(5):517-532.
[17]Kwon MY,Park E,Lee SJ,et al.Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death[J].Oncotarget,2015,6(27):24393-24403.
[18]Schott C,Graab U,Cuvelier N,et al.Oncogenic RAS mutants confer resistance of RMS13 rhabdomyosarcoma cells to oxidative stress-induced ferroptotic cell death[J].Front Oncol,2015,5:131.
[19]Sehm T,Fan Z,Ghoochani A,et al.Sulfasalazine impacts on ferroptotic cell death and alleviates the tumor microenvironment and glioma-induced brain edema[J].Oncotarget,2016,7(24):36021-36033.
[20]Liu Y,Wang W,Li Y,et al.The 5-lipoxygenase inhibitor zileuton confers neuroprotection against glutamate oxidative damage by inhibiting ferroptosis[J].Biol Pharm Bull,2015,38(8):1234-1239.
[21]Welin AK,Svedin P,Lapatto R,et al.Melatonin reduces inflammation and cell death in white matter in the mid-gestation fetal sheep following umbilical cord occlusion[J].Pediatr Res,2007,61(2):153-158.
[22]Skouta R,Dixon SJ,Wang J,et al.Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models[J].J Am Chem Soc,2014,136(12):4551-4556.
[23]Do Van B,Gouel F,Jonneaux A,et al.Ferroptosis,a newly characterized form of cell death in Parkinson’s disease that is regulated by PKC[J].Neurobiol Dis,2016,94:169-178.
[24]Chen L,Hambright WS,Na R,et al.Ablation of the ferroptosis inhibitor glutathione peroxidase 4 in neurons results in rapid motor neuron degeneration and paralysis[J].J Biol Chem,2015,290(47):28097-28106.
[25]Linkermann A,Skouta R,Himmerkus N,et al.Synchronized renal tubular cell death involves ferroptosis[J].Proc Natl Acad Sci U S A,2014,111(47):16836-16841.
[26]Gao M,Monian P,Quadri N,et al.Glutaminolysis and transferrin regulate ferroptosis[J].Mol Cell,2015,59(2):298-308.
[2]Dolma S,Lessnick SL,Hahn WC,et al.Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells[J].Cancer Cell,2003,3(3):285-296.
[3]Yang WS,Stockwell BR.Synthetic lethal screening identifies compounds activating iron-dependent,nonapoptotic cell death in oncogenic-RAS-harboring cancer cells[J].Chem Biol,2008,15(3):234-245.
[4]Yang WS,Stockwell BR.Ferroptosis:death by lipid peroxidation[J].Trends Cell Biol,2016,26(3):165-176.
[5]Friedmann Angeli JP,Schneider M,Proneth B,et al.Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice[J].Nat Cell Biol,2014,16(12):1180-1191.
[6]周彩虹,黄启福.凋亡与肿瘤及其治疗进展[J].中国病理生理杂志,2004,20(11):2124-2133.
[7]洪远,郭松雪,张建民.自噬在创伤性脑损伤中的作用[J].中国病理生理杂志,2011,27(8):1652-1656.
[8]Galluzzi L,Vitale I,Abrams JM,et al.Molecular definitions of cell death subroutines:recommendations of the Nomenclature Committee on Cell Death 2012[J].Cell Death Differ,2012,19(1):107-120.
[9]安鹏.铁代谢稳态失衡Hepcidin调控机制研究[D].上海:华东理工大学,2014.
[10]Bogdan AR,Miyazawa M,Hashimoto K,et al.Regulators of iron homeostasis:new players in metabolism,cell death,and disease[J].Trends Biochem Sci,2016,41(3):274-286.
[11]Tejedor JR,Papasaikas P,Valcarcel J.Genome-wide identification of Fas/CD95 alternative splicing regulators reveals links with iron homeostasis[J].Mol Cell,2015,57(1):23-38.
[12]Xie Y,Hou W,Song X,et al.Ferroptosis:process and function[J].Cell Death Differ,2016,23(3):369-379.
[13]Louandre C,Marcq I,Bouhlal H,et al.The retinoblastoma(Rb)protein regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma cells[J].Cancer Lett,2015,356(2 Pt B):971-977.
[14]Sun X,Ou Z,Chen R,et al.Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells[J].Hepatology,2016,63(1):173-184.
[15]Lorincz T,Jemnitz K,Kardon T,et al.Ferroptosis is involved in acetaminophen induced cell death[J].Pathol Oncol Res,2015,21(4):1115-1121.
[16]Eling N,Reuter L,Hazin J,et al.Identification of artesunate as a specific activator of ferroptosis in pancreatic cancer cells[J].Oncoscience,2015,2(5):517-532.
[17]Kwon MY,Park E,Lee SJ,et al.Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death[J].Oncotarget,2015,6(27):24393-24403.
[18]Schott C,Graab U,Cuvelier N,et al.Oncogenic RAS mutants confer resistance of RMS13 rhabdomyosarcoma cells to oxidative stress-induced ferroptotic cell death[J].Front Oncol,2015,5:131.
[19]Sehm T,Fan Z,Ghoochani A,et al.Sulfasalazine impacts on ferroptotic cell death and alleviates the tumor microenvironment and glioma-induced brain edema[J].Oncotarget,2016,7(24):36021-36033.
[20]Liu Y,Wang W,Li Y,et al.The 5-lipoxygenase inhibitor zileuton confers neuroprotection against glutamate oxidative damage by inhibiting ferroptosis[J].Biol Pharm Bull,2015,38(8):1234-1239.
[21]Welin AK,Svedin P,Lapatto R,et al.Melatonin reduces inflammation and cell death in white matter in the mid-gestation fetal sheep following umbilical cord occlusion[J].Pediatr Res,2007,61(2):153-158.
[22]Skouta R,Dixon SJ,Wang J,et al.Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models[J].J Am Chem Soc,2014,136(12):4551-4556.
[23]Do Van B,Gouel F,Jonneaux A,et al.Ferroptosis,a newly characterized form of cell death in Parkinson’s disease that is regulated by PKC[J].Neurobiol Dis,2016,94:169-178.
[24]Chen L,Hambright WS,Na R,et al.Ablation of the ferroptosis inhibitor glutathione peroxidase 4 in neurons results in rapid motor neuron degeneration and paralysis[J].J Biol Chem,2015,290(47):28097-28106.
[25]Linkermann A,Skouta R,Himmerkus N,et al.Synchronized renal tubular cell death involves ferroptosis[J].Proc Natl Acad Sci U S A,2014,111(47):16836-16841.
[26]Gao M,Monian P,Quadri N,et al.Glutaminolysis and transferrin regulate ferroptosis[J].Mol Cell,2015,59(2):298-308.