肝脏疾病中内质网应激与铁死亡的关系

叶露; 李秀芹; 王建青

doi:10.3969/j.issn.1001-5256.2023.04.036

肝脏疾病中内质网应激与铁死亡的关系

DOI: 10.3969/j.issn.1001-5256.2023.04.036

叶露^{1, 2, 3},
李秀芹^{1, 2},
王建青^{1, 2, , ,}

1.
安徽医科大学第一附属医院药学部，合肥 230012
2.
安徽省公共卫生临床中心，合肥 230012
3.
安徽医科大学药学院，合肥 230032

基金项目:

国家自然科学基金 (82073566);

安徽省高校优秀青年人才支持计划资助项目 (gxyq2019014);

临床药学与药理学共建项目 (2020)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：叶露负责查阅文章，撰写论文；李秀芹、王建青负责修改文章并最后定稿。

详细信息

通信作者:
王建青，jianqingwang81@126.com (ORCID: 0000-0002-7935-9520)

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出版历程
- 收稿日期: 2022-08-24
- 录用日期: 2022-10-08
- 出版日期: 2023-04-20

Association between endoplasmic reticulum stress and ferroptosis in liver diseases

Lu YE^{1, 2, 3},
Xiuqin LI^{1, 2},
Jianqing WANG^{1, 2
, ,
,}

1.
Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei 230012, China
2.
Anhui Public Health Clinical Center, Hefei 230012, China
3.
School of Pharmacy, Anhui Medical University, Hefei 230032, China

Research funding:

National Natural Science Foundation of China (82073566);

The Program of Excellent Young Talents in Universities of Anhui Province (gxyq2019014);

Clinical Pharmacy and Pharmacology (2020)

More Information

Corresponding author: WANG Jianqing, jianqingwang81@126.com (ORCID: 0000-0002-7935-9520)

摘要

摘要: 肝脏疾病的发病机制研究一直广受关注。内质网应激(ERS)是细胞的一种自我保护机制，但持续、严重的应激可诱导凋亡、自噬和铁死亡。其中，铁死亡作为近年研究热点，主要特征为铁依赖性脂质过氧化物的积累，在肝脏疾病的发生发展中发挥着关键作用，但目前关于肝脏疾病中ERS参与铁死亡的相关研究尚少。本文归纳了ERS相关信号通路和铁死亡的发生机制及其在肝脏疾病中的研究进展，为肝病治疗研究提供更多方向。
- 肝疾病 /
- 内质网应激 /
- 铁死亡
Abstract: Research on the pathogenesis of liver diseases has attracted great attention. Endoplasmic reticulum stress (ERS) is a self-protective mechanism of cells, but sustained and severe ERS can induce apoptosis, autophagy, and ferroptosis, among which ferroptosis has been a research hotspot in recent years. Ferroptosis is mainly characterized by the accumulation of iron-dependent lipid peroxides and plays a key role in the development and progression of liver diseases, but there are currently few studies on the involvement of ERS in ferroptosis in liver diseases. This article summarizes the research advances in ERS-related signaling pathways, the mechanism of ferroptosis, and the involvement of ERS in liver diseases, so as to provide more ideas for research on the treatment of liver diseases.
- Liver Diseases /
- Endoplasmic Reticulum Stress /
- Ferroptosis

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图 1 肝脏疾病中ERS与铁死亡的关系

Figure 1. Relationship between endoplasmic reticulum stress and ferroptosis in liver diseases

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参考文献(36)

[1]	WANG M, KAUFMAN RJ. Protein misfolding in the endoplasmic reticulum as a conduit to human disease[J]. Nature, 2016, 529(7586): 326-335. DOI: 10.1038/nature17041.
[2]	HETZ C, PAPA FR. The unfolded protein response and cell fate control[J]. Mol Cell, 2018, 69(2): 169-181. DOI: 10.1016/j.molcel.2017.06.017.
[3]	HAN CC, WAN FS. New insights into the role of endoplasmic reticulum stress in breast cancer metastasis[J]. J Breast Cancer, 2018, 21(4): 354-362. DOI: 10.4048/jbc.2018.21.e51.
[4]	UDDIN MS, TEWARI D, SHARMA G, et al. Molecular mechanisms of ER stress and UPR in the pathogenesis of alzheimer's disease[J]. Mol Neurobiol, 2020, 57(7): 2902-2919. DOI: 10.1007/s12035-020-01929-y.
[5]	HETZ C, ZHANG K, KAUFMAN RJ. Mechanisms, regulation and functions of the unfolded protein response[J]. Nat Rev Mol Cell Biol, 2020, 21(8): 421-438. DOI: 10.1038/s41580-020-0250-z.
[6]	KOPP MC, LARBURU N, DURAIRAJ V, et al. UPR proteins IRE1 and PERK switch BiP from chaperone to ER stress sensor[J]. Nat Struct Mol Biol, 2019, 26(11): 1053-1062. DOI: 10.1038/s41594-019-0324-9.
[7]	CALFON M, ZENG H, URANO F, et al. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA[J]. Nature, 2002, 415(6867): 92-96. DOI: 10.1038/415092a.
[8]	YOSHIDA H, MATSUI T, YAMAMOTO A, et al. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor[J]. Cell, 2001, 107(7): 881-891. DOI: 10.1016/s0092-8674(01)00611-0.
[9]	DONNELLY N, GORMAN AM, GUPTA S, et al. The eIF2α kinases: their structures and functions[J]. Cell Mol Life Sci, 2013, 70(19): 3493-3511. DOI: 10.1007/s00018-012-1252-6.
[10]	MAMADY H, STOREY KB. Coping with the stress: expression of ATF4, ATF6, and downstream targets in organs of hibernating ground squirrels[J]. Arch Biochem Biophys, 2008, 477(1): 77-85. DOI: 10.1016/j.abb.2008.05.006.
[11]	SANTAMARÍA PG, MAZÓN MJ, ERASO P, et al. UPR: An upstream signal to EMT induction in cancer[J]. J Clin Med, 2019, 8(5): 624. DOI: 10.3390/jcm8050624.
[12]	KIM JM, KIM JS, KIM N, et al. Helicobacter pylori vacuolating cytotoxin induces apoptosis via activation of endoplasmic reticulum stress in dendritic cells[J]. J Gastroenterol Hepatol, 2015, 30(1): 99-108. DOI: 10.1111/jgh.12663.
[13]	WALTER P, RON D. The unfolded protein response: from stress pathway to homeostatic regulation[J]. Science, 2011, 334(6059): 1081-1086. DOI: 10.1126/science.1209038.
[14]	SHORE GC, PAPA FR, OAKES SA. Signaling cell death from the endoplasmic reticulum stress response[J]. Curr Opin Cell Biol, 2011, 23(2): 143-149. DOI: 10.1016/j.ceb.2010.11.003.
[15]	DIXON SJ, LEMBERG KM, LAMPRECHT MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death[J]. Cell, 2012, 149(5): 1060-1072. DOI: 10.1016/j.cell.2012.03.042.
[16]	STOCKWELL BR, FRIEDMANN ANGELI JP, BAYIR H, et al. Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease[J]. Cell, 2017, 171(2): 273-285. DOI: 10.1016/j.cell.2017.09.021.
[17]	KAGAN VE, MAO G, QU F, et al. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis[J]. Nat Chem Biol, 2017, 13(1): 81-90. DOI: 10.1038/nchembio.2238.
[18]	JIANG L, HICKMAN JH, WANG SJ, et al. Dynamic roles of p53-mediated metabolic activities in ROS-induced stress responses[J]. Cell Cycle, 2015, 14(18): 2881-2885. DOI: 10.1080/15384101.2015.1068479.
[19]	JIANG L, KON N, LI T, et al. Ferroptosis as a p53-mediated activity during tumour suppression[J]. Nature, 2015, 520(7545): 57-62. DOI: 10.1038/nature14344.
[20]	CHEN D, FAN Z, RAUH M, et al. ATF4 promotes angiogenesis and neuronal cell death and confers ferroptosis in a xCT-dependent manner[J]. Oncogene, 2017, 36(40): 5593-5608. DOI: 10.1038/onc.2017.146.
[21]	XU M, TAO J, YANG Y, et al. Ferroptosis involves in intestinal epithelial cell death in ulcerative colitis[J]. Cell Death Dis, 2020, 11(2): 86. DOI: 10.1038/s41419-020-2299-1.
[22]	PARK EJ, PARK YJ, LEE SJ, et al. Whole cigarette smoke condensates induce ferroptosis in human bronchial epithelial cells[J]. Toxicol Lett, 2019, 303: 55-66. DOI: 10.1016/j.toxlet.2018.12.007.
[23]	WANG CE, XU WT, GONG J, et al. Progress in the treatment of nonalcoholic fatty liver disease[J]. Clin J Med Offic, 2022, 50(9): 897-899, 903. DOI: 10.16680/j.1671-3826.2022.09.06. 王彩娥, 许文涛, 宫建, 等. 非酒精性脂肪性肝病治疗研究进展[J]. 临床军医杂志, 2022, 50(9): 897-899, 903. DOI: 10.16680/j.1671-3826.2022.09.06.
[24]	JIANG Y, HUANG JM, LIANG YZ, et al. Basic study on the mechanism of iron death in non-alcoholic fatty liver disease[J]. J Guangxi Med Univ, 2022, 39(1): 13-20. DOI: 10.16190/j.cnki.45-1211/r.2022.01.003. 姜嫄, 黄锦明, 梁瑜祯, 等. 非酒精性脂肪性肝病铁死亡机制的基础研究[J]. 广西医科大学学报, 2022, 39(1): 13-20. DOI: 10.16190/j.cnki.45-1211/r.2022.01.003.
[25]	WEI S, QIU T, WANG N, et al. Ferroptosis mediated by the interaction between Mfn2 and IREα promotes arsenic-induced nonalcoholic steatohepatitis[J]. Environ Res, 2020, 188: 109824. DOI: 10.1016/j.envres.2020.109824.
[26]	WANG KJ, HUANG ZH, SHI QL, et al. Research progress of precise hepatectomy for hepatocellular carcinoma[J]. China Med Herald, 2021, 18(23): 43-46. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202123010.htm 王克净, 黄祖鸿, 石清兰, 等. 肝细胞癌精准肝切除的研究进展[J]. 中国医药导报, 2021, 18(23): 43-46. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202123010.htm
[27]	HASSANNIA B, VANDENABEELE P, VANDEN BERGHE T. Targeting ferroptosis to iron out cancer[J]. Cancer Cell, 2019, 35(6): 830-849. DOI: 10.1016/j.ccell.2019.04.002.
[28]	WANG Z, LI M, LIU Y, et al. Dihydroartemisinin triggers ferroptosis in primary liver cancer cells by promoting and unfolded protein response-induced upregulation of CHAC1 expression[J]. Oncol Rep, 2021, 46(5): 240. DOI: 10.3892/or.2021.8191.
[29]	SPYCHALSKI P, KOBIELA J, ANTOSZEWSKA M, et al. Patient specific outcomes of charged particle therapy for hepatocellular carcinoma - A systematic review and quantitative analysis[J]. Radiother Oncol, 2019, 132: 127-134. DOI: 10.1016/j.radonc.2018.12.012.
[30]	ZHENG X, LIU B, LIU X, et al. PERK regulates the sensitivity of hepatocellular carcinoma cells to high-LET carbon ions via either apoptosis or ferroptosis[J]. J Cancer, 2022, 13(2): 669-680. DOI: 10.7150/jca.61622.
[31]	KANG R, KROEMER G, TANG D. The tumor suppressor protein p53 and the ferroptosis network[J]. Free Radic Biol Med, 2019, 133: 162-168. DOI: 10.1016/j.freeradbiomed.2018.05.074.
[32]	WANG YW, LIANG YR. Research progress on liver transplantation for drug-induced liver injury[J]. Ogran Transplant, 2022, 13(3): 338-343. DOI: 10.3969/j.issn.1674-7445.2022.03.009. 王砚伟, 梁雨荣. 药物性肝损伤肝移植治疗进展[J]. 器官移植, 2022, 13(3): 338-343. DOI: 10.3969/j.issn.1674-7445.2022.03.009.
[33]	TAK J, KIM YS, KIM TH, et al. Gα12 overexpression in hepatocytes by ER stress exacerbates acute liver injury via ROCK1-mediated miR-15a and ALOX12 dysregulation[J]. Theranostics, 2022, 12(4): 1570-1588. DOI: 10.7150/thno.67722.
[34]	European Association for the Study of the Liver. EASL clinical practice guidelines: Management of alcohol-related liver disease[J]. J Hepatol, 2018, 69(1): 154-181. DOI: 10.1016/j.jhep.2018.03.018.
[35]	CZAJA AJ. Review article: iron disturbances in chronic liver diseases other than haemochromatosis - pathogenic, prognostic, and therapeutic implications[J]. Aliment Pharmacol Ther, 2019, 49(6): 681-701. DOI: 10.1111/apt.15173.
[36]	MUELLER K, SUNAMI Y, STUETZLE M, et al. CHOP-mediated hepcidin suppression modulates hepatic iron load[J]. J Pathol, 2013, 231(4): 532-542. DOI: 10.1002/path.4221.