2,5-Hexanedione induces apoptosis via a mitochondria-mediated pathway in PC12 cells

被引:4
作者
Qi, Yuan [1 ]
Li, Shuang-yue [1 ]
Piao, Feng-yuan [1 ]
Wang, Zhe-min [1 ]
Chen, Ruo-lin [1 ]
Liu, Shuang [1 ]
Shen, Jing-shun [2 ]
机构
[1] Dalian Med Univ, Dept Occupat & Environm Hlth, Dalian 116044, Peoples R China
[2] Dalian Med Univ, Affiliated Hosp 1, Dept Neurol, Dalian 116044, Peoples R China
基金
中国国家自然科学基金;
关键词
2,5-Hexanedione; Apoptosis; PC12; cells; Mitochondria-mediated pathway; Neurotoxicity; BCL-2 FAMILY PROTEINS; N-HEXANE; NEURONAL APOPTOSIS; OXIDATIVE STRESS; CANCER CELLS; DEATH; CASPASE-3; EXPOSURE; RATS; BAX;
D O I
10.1007/s13273-015-0010-x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
2,5-Hexanedione (HD) is the main active metabolite of n-hexane and mediates the neurotoxicity of the parent compound. Studies suggested that apoptosis involved in HD neurotoxicity. However, the mechanism of HD-induced neuronal apoptosis remains unknown. To explore its underlying mechanism, we treated PC12 cells with 5, 10 and 20 mM HD for 24 h, respectively. We found that HD induced apoptotic death in PC12 cells in a dose-dependent manner. Moreover, HD down-regulated Bcl-2 expression, up-regulated Bax expression and Bax/Bcl-2 ratio, promoted the disruption of mitochondrial transmembrane potential, induced the release of cytochrome c from mitochondria, and increased the activity of caspase-3 in PC12 cells, which were all the key regulators of intrinsic apoptotic pathway. These results indicate that HD induces apoptosis via a mitochondria-mediated pathway in PC12 cells.
引用
收藏
页码:79 / 87
页数:9
相关论文
共 40 条
[1]  
ABBRITTI G, 1976, BRIT J IND MED, V33, P92
[2]   Born to be alive: a role for the BCL-2 family in melanoma tumor cell survival, apoptosis, and treatment [J].
Anvekar, Rina A. ;
Asciolla, James J. ;
Missert, Derek J. ;
Chipuk, Jerry E. .
FRONTIERS IN ONCOLOGY, 2011, 1
[3]   Mechanism of Alternariol monomethyl ether-induced mitochondrial apoptosis in human colon carcinoma cells [J].
Bensassi, Fatma ;
Gallerne, Cindy ;
el Dein, Ossama Sharaf ;
Hajlaoui, Mohamed Rabeh ;
Bacha, Hassen ;
Lemaire, Christophe .
TOXICOLOGY, 2011, 290 (2-3) :230-240
[4]   A comparison of the apoptotic and cytotoxic effects of hexanedione derivatives on human non-neuronal lines and the neuroblastoma line SH-SY5Y [J].
Coleman, Michael D. ;
Zilz, Thomas R. ;
Griffiths, Helen R. ;
Woehrling, Elizabeth K. .
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, 2008, 102 (01) :25-29
[5]   TOXICITY AND METABOLISM OF THE NEUROTOXIC HEXACARBONS NORMAL-HEXANE, 2-HEXANONE, AND 2,5-HEXANEDIONE [J].
COURI, D ;
MILKS, M .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1982, 22 :145-166
[6]   Expression of Bcl-2, Bax and Caspase-3 in nerve tissues of rats chronically exposed to 2,5-hexanedione [J].
Cui, Ning ;
Li, Shanxia ;
Zhao, Xiulan ;
Zhang, Tianliang ;
Zhang, Cuili ;
Yu, Lihua ;
Zhu, Zhengping ;
Xie, Keqin .
NEUROCHEMICAL RESEARCH, 2007, 32 (09) :1566-1572
[7]   Evaluation of 2,5-hexanedione in urine of workers exposed to n-hexane in Brazilian shoe factories [J].
dos Santos, CR ;
Passarelli, MM ;
Nascimento, ED .
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2002, 778 (1-2) :237-244
[8]   MiADMSA reverses impaired mitochondrial energy metabolism and neuronal apoptotic cell death after arsenic exposure in rats [J].
Dwivedi, Nidhi ;
Mehta, Ashish ;
Yadav, Abhishek ;
Binukumar, B. K. ;
Gill, Kiran Dip ;
Flora, Swaran J. S. .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 2011, 256 (03) :241-248
[9]   Apoptosis: A review of programmed cell death [J].
Elmore, Susan .
TOXICOLOGIC PATHOLOGY, 2007, 35 (04) :495-516
[10]   The Proapoptotic BH3-Only, Bcl-2 Family Member, Puma Is Critical for Acute Ethanol-Induced Neuronal Apoptosis [J].
Ghosh, Arindam P. ;
Walls, Ken C. ;
Klocke, Barbara J. ;
Toms, Rune ;
Strasser, Andreas ;
Roth, Kevin A. .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2009, 68 (07) :747-756