title: 3-Monochloro-1,2-propanediol (3-MCPD) induces apoptosis via mitochondrial oxidative phosphorylation system impairment and the caspase cascade pathway.
abstract: 3-Monochloro-1,2-propanediol (3-MCPD) is the most toxic chloropropanols compounds in foodstuff which mainly generated during thermal processing. Kidney is one of the primary target organs for 3-MCPD. Using human embryonic kidney cell (HEK293FT) as an in vitro model, we found that 3-MCPD caused concentration-dependent increase in cytoxicity as assessed by dye uptake, lactatedehydrogenase (LDH) leakage and MTT assays. HEK293FT cell treated with 3-MCPD suffered the decrease of mitochondrial membrane potential and the impairment of mitochondrial oxidative phosphorylation system, especially the reduced amount of mRNA expression and protein synthesis of electron transport chain complex II, complex IV, and complex III. More importantly, energy release (ATP synthesis) was significantly inhibited by 3-MCPD resulting from the down regulation expressions of ATP synthase (ATP6 and ATP8), as well as the loss of transmembrane potential required for synthesis of ATP. The decreased ratio of mitochondrial apoptogenic factors Bax/Bcl-2 and the cytochrome-c release from mitochondria to cytosol followed by the activation of apoptotic initiators caspase 9 and apoptotic executioners (caspase 3, caspase 6 and caspase 7) leading to apoptosis. The activation of caspase 8 and caspase 2 implied that there were probably other factors to induce the caspase-dependent apoptosis.
authors.affiliation: College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanixi, 712100, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Peng
authors.affiliation: College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanixi, 712100, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gan
authors.affiliation: Institute of Food Science and Genetic Engineering, Harbin Institute of Technology, Harbin, Heilongjiang, 150086, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanixi, 712100, China.
authors.forename: Zhenqiang
authors.initials: Z
authors.lastname: Shi
authors.affiliation: College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanixi, 712100, China. Electronic address: foodscixiaodong@yahoo.com.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xia
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002629:Chemosterilants / Q000633:toxicity*; D004579:Electron Transport / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000517:alpha-Chlorohydrin / Q000633:toxicity*
chemical_list: D002629:Chemosterilants; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D000517:alpha-Chlorohydrin; D020169:Caspases
keywords: 3-MCPD; ATP synthesis; Apoptosis; Caspase; Human embryonic kidney cell; Mitochondrial oxidative phosphorylation