Protection of cells from menadione-induced apoptosis by inhibition of lipid peroxidation.

Abstract

Menadione is a commonly used compound that causes oxidative stress. We investigated the influence of lipid peroxidation on the apoptotic response of mouse myogenic C2C12 cells following menadione-induced oxidative stress. The presence of hypodiploid cells and phosphatidylserine translocation were assayed to detect apoptotic cells. Menadione at 10-40 micro M induced cell apoptosis. Menadione at dose of 80 micro M induced both apoptosis and necrosis. At a 160 micro M dosage, menadione induced cell necrosis. Caspase 3 activation is required for menadione-induced apoptosis. Incubation of cells with 40 micro M menadione resulted in the depletion of cellular glutathione and increased lipid peroxidation. Pre-treatment of cells with cysteine suppressed the menadione-induced apoptosis and prevented changes in reactive oxygen species levels, glutathione levels and lipid peroxidation. Pre-treatment of cells with deferoxamine mesylate, an iron chelator, also reduced both menadione-induced apoptosis and lipid peroxidation. However, this did not prevent menadione-induced glutathione depletion. Thus, the inhibition of lipid peroxidation by deferoxamine mesylate prevented apoptosis even though cellular glutathione remained depleted. Our data suggest that menadione-induced apoptosis is directly linked to iron-dependent lipid peroxidation.

• Authors: Tzeon-Jye Chiou, Sin-Tak Chu, Woan-Fang Tzeng
• Journal: Toxicology (Toxicology) Vol. 191 Issue 2-3 Pg. 77-88 (Sep 30 2003) ISSN: 0300-483X [Print] Ireland
• PMID: 12965111 (Publication Type: Journal Article)

Chemical References

• Iron Chelating Agents
• Lipid Peroxides
• Reactive Oxygen Species
• Vitamin K 3
• Casp3 protein, mouse
• Caspase 3
• Caspases
• Glutathione
• Deferoxamine
• Cysteine

Topics

• Animals
• Apoptosis (drug effects, physiology)
• Caspase 3
• Caspases (metabolism)
• Cysteine (pharmacology)
• Deferoxamine (pharmacology)
• Drug Interactions
• Flow Cytometry
• Glutathione (antagonists & inhibitors, metabolism)
• Iron Chelating Agents (pharmacology)
• Lipid Peroxidation (drug effects)
• Lipid Peroxides (metabolism)
• Mice
• Muscle, Skeletal (cytology, drug effects, metabolism)
• Myoblasts (cytology, drug effects, metabolism)
• Necrosis
• Oxidative Stress (physiology)
• Ploidies
• Reactive Oxygen Species (metabolism)
• Vitamin K 3 (antagonists & inhibitors, toxicity)