Apoptosis Induced by Manganese on Neuronal SK-N-MC Cell Line: Endoplasmic Reticulum (ER) Stress and Mitochondria Dysfunction.
- Author:
Hyonok YOON
1
;
Do Sung KIM
;
Geum Hwa LEE
;
Kee Won KIM
;
Hyung Ryong KIM
;
Han Jung CHAE
Author Information
1. Department of Pharmacology, School of Medicine, Chonbuk National University, Jeonju, Korea. hjchae@chonbuk.ac.kr
- Publication Type:Original Article
- Keywords:
Apoptosis;
Endoplasmic reticulum stress;
Manganese chloride (MnCl2);
Mitochondria dysfunction
- MeSH:
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
- From:Environmental Health and Toxicology
2011;26(1):e2011017-
- CountryRepublic of Korea
- Language:English
-
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.
