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Mitochondrial control of apoptosis through modulation of cardiolipin oxidation in hepatocellular carcinoma: A novel link between oxidative stress and cancer

文献类型：期刊论文

作者Zhong, Huiqin2,3; Xiao, Mengqing2,3; Zhu, Mingjiang2; Sa, Rina2,3; Lu, Jianhong2,3; Tao, Yongzhen2; Chen, Qun2,3; Xia, Lin2; Yin, Huiyong2,3,8; Zarkovic, Kamelija4,5
刊名FREE RADICAL BIOLOGY AND MEDICINE
出版日期2017
卷号102期号:-页码:67-76
关键词Hepatocellular carcinoma Oxidative stress Cardiolipin 4-hydroxy-2-nonenal Apoptosis
ISSN号0891-5849
DOI10.1016/j.freeradbiomed.2016.10.494
文献子类Article
英文摘要Altered redox status in cancer cells has been linked to lipid peroxidation induced by reactive oxygen species (ROS) and subsequent formation of reactive lipid electrophiles, especially 4-hydroxy-nonenal (4-HNE). Emerging evidence suggests that cancer cells manipulate redox status to acquire anti-apoptotic phenotype but the underlying mechanisms are poorly understood. Cardiolipin (CL), a mitochondria-specific inner membrane phospholipid, is critical for maintaining mitochondrial function. Paradoxically, liver tissues contain tetralinoleoyl cardiolipin (TLCL) as the major CL in mitochondria yet emerging evidence suggests that ROS generated in mitochondria may lead to CL peroxidation and activation of intrinsic apoptosis. It remains unclear how CL oxidation leads to apoptosis and its relevance to the pathogenesis of hepatocellular carcinoma (HCC). We employed a mass spectrometry-based lipidomic approach to profile lipids in human tissues of HCC and found that CL was gradually decreased in tumor comparing to peripheral non-cancerous tissues, accompanied by a concomitant decrease of oxidized CL and its oxidation product, 4-HNE. Incubation of liver cancer cells with TLCL significantly restored apoptotic sensitivity accompanied by an increase of CL and its oxidation products when treated with staurosporine (STS) or Sorafenib (the standard treatment for late stage HCC patients). Our studies uncovered a novel mechanism by which cancer cells adopt to evade apoptosis, highlighting the importance of mitochondrial control of apoptosis through modulation of CL oxidation and subsequent 4-HNE formation in HCC. Thus manipulation of mitochondrial CL oxidation and lipid electrophile formation may have potential therapeutic value for diseases linked to oxidative stress and mitochondrial dysfunctions.
学科主题Biochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS关键词LIPID-PEROXIDATION ; CELL-DEATH ; SHOTGUN LIPIDOMICS ; BIOLOGICAL SAMPLES ; IN-VITRO ; MECHANISMS ; METABOLISM ; SORAFENIB ; ASYMMETRY ; PROTEINS
语种英语
WOS记录号WOS:000392361200006
出版者ELSEVIER SCIENCE INC
版本出版稿
源URL[http://202.127.25.144/handle/331004/1209]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Karl Franz Univ Graz, Inst Mol Biosci, Graz, Austria;
2.Chinese Acad Sci, Shanghai Inst Biol Sci, INS, Key Lab food safety Res, Shanghai 200031, Peoples R China;
3.Univ Chinese Acad Sci, CAS, Beijing, Peoples R China;
4.Univ Zagreb, Clin Hosp Ctr, Div Pathol, Zagreb 41000, Croatia;
5.Univ Zagreb, Fac Med, Zagreb 41000, Croatia;
6.Minist Hlth, Key Lab food safety risk Assessment, Beijing, Peoples R China;
7.Eastern Hepatobiliary Surg Hosp, Shanghai, Peoples R China;
8.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China,
9.Rudjer Boskovic Inst, Lab Oxidat Stress, Zagreb, Croatia;
推荐引用方式
GB/T 7714		 Zhong, Huiqin,Xiao, Mengqing,Zhu, Mingjiang,et al. Mitochondrial control of apoptosis through modulation of cardiolipin oxidation in hepatocellular carcinoma: A novel link between oxidative stress and cancer[J]. FREE RADICAL BIOLOGY AND MEDICINE,2017,102(-):67-76.
APA Zhong, Huiqin.,Xiao, Mengqing.,Zhu, Mingjiang.,Sa, Rina.,Lu, Jianhong.,...&,.(2017).Mitochondrial control of apoptosis through modulation of cardiolipin oxidation in hepatocellular carcinoma: A novel link between oxidative stress and cancer.FREE RADICAL BIOLOGY AND MEDICINE,102(-),67-76.
MLA Zhong, Huiqin,et al."Mitochondrial control of apoptosis through modulation of cardiolipin oxidation in hepatocellular carcinoma: A novel link between oxidative stress and cancer".FREE RADICAL BIOLOGY AND MEDICINE 102.-(2017):67-76.

入库方式： OAI收割

来源：上海营养与健康研究所

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