Toxic effects of microcystin-LR on the HepG2 cell line under hypoxic and normoxic conditions.

Abstract

Microcystins (MCs) are highly liver-specific and evidenced as a liver tumor promoter. Oxidative stress is one of the most important toxicity mechanisms of MCs, which is tightly related to oxygen concentration. The effects of MCs on animals and cell lines in normoxia and the mechanisms have been well studied, but such effects in different oxygen conditions were still unclear. The aim of the present study was to explore the cellular response of the human hepatocellular carcinoma cell line (HepG2) to MC-LR exposure under hypoxic (1% O2 ) and normoxic (21% O2 ) conditions. We examined cell viability, mitochondrial membrane potential (MMP), superoxide dismutase (SOD) activity and gene expression posttoxin exposure. Cell viability was increased by MC-LR in normoxia although decreased in hypoxia. MC-LR markedly induced MMP loss under hypoxic condition but only slightly MMP loss under normoxic condition. SOD activity was significantly induced by MC-LR in hypoxia, indicating prolonged oxidative stress. Inhibitory apoptosis protein (c-IAP2) was significantly up-regulated by MC-LR under normoxic condition, suggesting that c-IAP2 played an important role in the promotion of cell proliferation by MC-LR. These results indicate that MC-LR promotes cell proliferation under normoxic condition whereas induces cell apoptosis under hypoxic condition.

• Authors: Xin Zhang, Ping Xie, Xuezhen Zhang, Wenshan Zhou, Sujuan Zhao, Yanyan Zhao, Yan Cai
• Journal: Journal of applied toxicology : JAT (J Appl Toxicol) Vol. 33 Issue 10 Pg. 1180-6 (Oct 2013) ISSN: 1099-1263 [Electronic] England
• PMID: 22539157 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 John Wiley & Sons, Ltd.

Chemical References

• BAX protein, human
• Carcinogens
• Marine Toxins
• Microcystins
• TP53 protein, human
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• Superoxide Dismutase
• CASP3 protein, human
• Caspase 3
• cyanoginosin LR
• Oxygen

Topics

• Apoptosis (drug effects)
• Carcinogens (toxicity)
• Caspase 3 (genetics, metabolism)
• Cell Hypoxia
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Hep G2 Cells
• Humans
• Liver (cytology, drug effects, pathology)
• Marine Toxins
• Membrane Potential, Mitochondrial (drug effects)
• Microcystins (toxicity)
• Oxidative Stress (drug effects)
• Oxygen (metabolism)
• Superoxide Dismutase (metabolism)
• Tumor Suppressor Protein p53 (genetics, metabolism)
• bcl-2-Associated X Protein (genetics, metabolism)