Environ Health Toxicol.  2011 ;26(1):e2011017.

Apoptosis Induced by Manganese on Neuronal SK-N-MC Cell Line: Endoplasmic Reticulum (ER) Stress and Mitochondria Dysfunction

• Yoon H
• Kim DS
• Lee GH
• Kim KW
• Kim HR
• Chae HJ

Abstract

OBJECTIVES
Manganese chloride (MnCl2) is one of heavy metals for causing neurogenerative dysfunction like Manganism. The purpose of this study was to determine the acute toxicity of MnCl2 using different times and various concentrations including whether manganese toxicity may involve in two intrinsic pathways, endoplasmic reticulum (ER) stress and mitochondria dysfunction and lead to neuronal apoptosis mediated by organelle disorders in neuroblastoma cell line SK-N-MC.
METHODS
In the acute toxicity test, five concentrations (200, 400, 600, 800, 1,000 uM) of MnCl2 with 3, 6, 12, 24, 48 hours exposure were selected to analyze cell viability. In addition, to better understand their toxicity, acute toxicity was examined with 1,000 uM MnCl2 for 24 hours exposure via reactive oxygen species (ROS), mitochondria membrane potential, western blotting and mitochondrial complex activities.
RESULTS
Our results showed that both increments of dose and time prompt the increments in the number of dead cells. Cells treated by 1,000 microM MnCl2 activated 265% (+/-8.1) caspase-3 compared to control cell. MnCl2 induced intracellular ROS produced 168% (+/-2.3%) compared to that of the control cells and MnCl2 induced neurotoxicity significantly dissipated 48.9% of mitochondria membrane potential compared to the control cells.
CONCLUSIONS
This study indicated that MnCl2 induced apoptosis via ER stress and mitochondria dysfunction. In addition, MnCl2 affected only complex I except complex II, III or IV activities.

Keyword

Apoptosis; Endoplasmic reticulum stress; Manganese chloride (MnCl2); Mitochondria dysfunction

MeSH Terms

Apoptosis
Blotting, Western
Caspase 3
Cell Line
Cell Survival
Chlorides
Endoplasmic Reticulum
Endoplasmic Reticulum Stress
Manganese
Manganese Compounds
Membrane Potentials
Metals, Heavy
Mitochondria
Neuroblastoma
Neurons
Organelles
Reactive Oxygen Species
Toxicity Tests, Acute
Caspase 3
Chlorides
Manganese
Manganese Compounds
Metals, Heavy
Reactive Oxygen Species