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

doi:10.1016/j.freeradbiomed.2016.10.494

	Mitochondrial control of apoptosis through modulation of cardiolipin oxidation in hepatocellular carcinoma: A novel link between oxidative stress and cancer
	Zhong, Huiqin 1,2; Xiao, Mengqing1,2,9 ; Zarkovic, Kamelija 3,4; Zhu, Mingjiang 1; Sa, Rina 1,2; Lu, Jianhong 1,2; Tao, Yongzhen 1; Chen, Qun 1,2; Xia, Lin 1; Cheng, Shuqun 6; Waeg, Georg 7; Zarkovic, Neven 8; Yin, Huiyong1,2,5,9
	2017-01
发表期刊	FREE RADICAL BIOLOGY AND MEDICINE (IF:7.1[JCR-2023],7.9[5-Year])
ISSN	0891-5849
卷号	102 页码:67-76
发表状态	已发表
DOI	10.1016/j.freeradbiomed.2016.10.494
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.
关键词	Hepatocellular carcinoma Oxidative stress Cardiolipin 4-hydroxy-2-nonenal Apoptosis
收录类别	SCI
语种	英语
资助项目	Hundred Talents Program from CAS[2012OHTP07]
WOS研究方向	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS类目	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS记录号	WOS:000392361200006
出版者	ELSEVIER SCIENCE INC
WOS关键词	SHOTGUN LIPIDOMICS ; IN-VITRO ; CELLS ; MECHANISMS ; PEROXIDATION ; METABOLISM ; SORAFENIB ; ASYMMETRY ; EXTRACTS ; ACID
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1580
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_尹慧勇组生命科学与技术学院_硕士生
通讯作者	Yin, Huiyong
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, INS, Key Lab Food Safety Res, Shanghai 200031, Peoples R China 2.Univ Chinese Acad Sci, CAS, Beijing, Peoples R China 3.Univ Zagreb, Clin Hosp Ctr, Div Pathol, Zagreb 41000, Croatia 4.Univ Zagreb, Fac Med, Zagreb 41000, Croatia 5.Minist Hlth, Key Lab Food Safety Risk Assessment, Beijing, Peoples R China 6.Eastern Hepatobiliary Surg Hosp, Shanghai, Peoples R China 7.Karl Franz Univ Graz, Inst Mol Biosci, Graz, Austria 8.Rudjer Boskovic Inst, Lab Oxidat Stress, Zagreb, Croatia 9.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Zhong, Huiqin,Xiao, Mengqing,Zarkovic, Kamelija,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.,Zarkovic, Kamelija.,Zhu, Mingjiang.,Sa, Rina.,...&Yin, Huiyong.(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.