title: An iTRAQ-based mitoproteomics approach for profiling the nephrotoxicity mechanisms of ochratoxin A in HEK 293 cells.
abstract: Nephrotoxicity is the most prominent of ochratoxin A (OTA) among the diverse range of toxicological effects. Previous work indicated that reactive oxygen species (ROS) play an important role in the pathogenesis of a variety of renal diseases, and its major endogenous source is mitochondria. No research has used global protein expression profiling to investigate potential toxicity mechanisms of OTA at the mitochondria level. An iTRAQ-based mitoproteomics approach was used to explore possible toxicity mechanisms of OTA and potential protective mechanisms of N-acetyl-L-cysteine (NAC) using the mitochondria of Human Embryonic Kidney 293 (HEK 293) cells. Our results showed that OTA induced a decrease in ΔΨm, and an increase in ROS and cell death. We identified a total of 1973 nonredundant proteins, among which 1398 proteins (70.86%) were overlapped. There were 66 significantly different proteins expressed in response to OTA, which were mainly involved in the perturbation of the mitochondrial electron transport chain (mETC), inhibition of protein synthesis, and induction of stress response and cell death. In addition, NAC could almost completely reverse the adverse effects of OTA at the protein level. Finally, a hypothetical model of OTA-induced mitochondria damage is proposed to provide a framework for the toxicity mechanism of OTA.
authors.affiliation: Laboratory of food safety and molecular biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China.
authors.forename: Xiao Li
authors.initials: XL
authors.lastname: Shen
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wentao
authors.initials: W
authors.lastname: Xu
authors.forename: Rui
authors.initials: R
authors.lastname: Liang
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Zheng
authors.forename: YunBo
authors.initials: Y
authors.lastname: Luo
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Kunlun
authors.initials: K
authors.lastname: Huang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000009:adverse effects* / Q000494:pharmacology; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D008954:Models, Biological; D009793:Ochratoxins / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D045222:Electron Transport Chain Complex Proteins; D016166:Free Radical Scavengers; D024101:Mitochondrial Proteins; D009793:Ochratoxins; C025589:ochratoxin A; D000111:Acetylcysteine