Mitochondrial proteomic analysis reveals the molecular mechanisms underlying reproductive toxicity of zearalenone in MLTC-1 cells.

Abstract

Zearalenone (ZEA), a Fusarium mycotoxin that contaminates cereal crops worldwide, has been shown to affect the male reproductive system and trigger reactive oxygen species (ROS) generation. However, the mechanisms of its toxicity have not been fully understood. Because mitochondrion is a key organelle involved in producing ROS and generating metabolic intermediates for biosynthesis, an iTRAQ-based mitoproteomics approach was employed to identify the molecular mechanism of zearalenone toxicity using mitochondria of mouse Leydig tumor cells (MLTC-1). A total of 2014 nonredundant proteins were identified, among which 1401 proteins (69.56%) were overlapped. There were 52 differentially expressed proteins in response to ZEA, and they were primarily involved in energy metabolism, molecular transport and endocrine-related functions. Consistent with mitochondrial proteomic analysis, the ATP and intracellular Ca(2+) levels increased after ZEA treatment. The results suggest that lipid metabolism changed significantly after low-dose ZEA exposure, resulting in two alterations. One is the increase in energy production through promoted fatty acid uptake and β-oxidation, along with excessive oxidative stress; the other is an inhibition of steroidogenesis and esterification, possibly resulting in reduced hormone secretion. A hypothetical model of ZEA-induced mitochondrial damage is proposed to provide a framework for the mechanism of ZEA toxicity.

• Authors: Yuzhe Li, Boyang Zhang, Kunlun Huang, Xiaoyun He, YunBo Luo, Rui Liang, Haoshu Luo, Xiao Li Shen, Wentao Xu
• Journal: Toxicology (Toxicology) Vol. 324 Pg. 55-67 (Oct 03 2014) ISSN: 1879-3185 [Electronic] Ireland
• PMID: 25058043 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Mitochondrial Proteins
• Reactive Oxygen Species
• Testosterone
• Zearalenone
• Adenosine Triphosphate
• Calcium

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Calcium (metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Chromatography, High Pressure Liquid
• Databases, Protein
• Dose-Response Relationship, Drug
• Energy Metabolism (drug effects)
• Leydig Cell Tumor (metabolism, pathology)
• Lipid Metabolism (drug effects)
• Male
• Membrane Potential, Mitochondrial (drug effects)
• Mice
• Mitochondria (drug effects, metabolism, pathology)
• Mitochondrial Proteins (metabolism)
• Oxidative Stress (drug effects)
• Proteomics (methods)
• Reactive Oxygen Species (metabolism)
• Reproduction (drug effects)
• Tandem Mass Spectrometry
• Testosterone (metabolism)
• Zearalenone (toxicity)