title: Pathway of 3-MCPD-induced apoptosis in human embryonic kidney cells.
abstract: 3-Chloropropane-1,2-diol (3-MCPD) is a heat-produced contaminant formed during the preparation of soy sauce worldwide. The present investigation was conducted to determine the molecular aspects of 3-MCPD toxicity on human embryonic kidney cells (HEK293). Cell viability and apoptosis were assessed in response to exposure to 3-MCPD using the MTT assay and high-content screening (HCS). DNA damage, intracellular reactive oxygen species (ROS) and apoptosis-related proteins were evaluated. Genes related with apoptosis were detected by qPCR-array for further understanding the 3-MCPD induced cell apoptosis signaling pathway. Our results clearly showed that 3-MCPD treatment inhibits cell proliferation and reactive oxygen species generation. qPCR-array indicated that nine apoptotic genes were up-regulated more than 2-fold and six down-regulated more than 2-fold. Genes associated with the mitochondrial apoptotic pathway, especially BCL2 family genes, changed significantly, indicating that the mitochondrial apoptotic pathway is activated. Death receptor pathway-related genes, TNFRSF11B and TNFRSF1A, changed significantly, indicating that the death receptor pathway is also activated, resulting in the inhibition of cell growth and proliferation as well as induction of apoptosis. To sum up, the experiment results indicated that 3-MCPD induced HEK293 cell toxicity through the death receptor pathway and mitochondrial pathway.
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science of Jiangnan University, School of Food Science Synergetic Innovation Center of Food Safety and Nutrition, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ji
authors.forename: Pei
authors.initials: P
authors.lastname: Zhu
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.forename: Jiadi
authors.initials: J
authors.lastname: Sun
authors.forename: Lu
authors.initials: L
authors.lastname: An
authors.forename: Yinzhi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiulan
authors.initials: X
authors.lastname: Sun
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage; D005506:Food Contamination; D057809:HEK293 Cells; D006801:Humans; D053244:Osteoprotegerin / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000517:alpha-Chlorohydrin / Q000633:toxicity*
chemical_list: D053244:Osteoprotegerin; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D047888:Receptors, Tumor Necrosis Factor, Type I; C506030:TNFRSF11B protein, human; C506235:TNFRSF1A protein, human; D016159:Tumor Suppressor Protein p53; D045304:Cytochromes c; D000517:alpha-Chlorohydrin; D020169:Caspases