Korean J Physiol Pharmacol.  2000 Feb;4(1):47-54.

Transition metal induces apoptosis in MC3T3E1 osteoblast: Evidence of free radical release

Affiliations
  • 1Department of Dental Pharmacology, School of Dentistry, Wonkwang University, Iksan, Chonbuk, South Korea.

Abstract

Transition metal ions including Se2+, Cd2+, Hg2+ or Mn2+ have been thought to disturb the bone metabolism directly. However, the mechanism for the bone lesion is unknown. In this study, we demonstrated that MC3T3E1 osteoblasts, exposed to various transition metal ions; selenium, cadmium, mercury or manganese, generated massive amounts of reactive oxygen species (ROS). The released ROS were completely quenched by free radical scavengers-N-acetyl cysteine (NAC), reduced glutathione (GSH), or superoxide dismutase (SOD). First, we have observed that selenium (10 micrometer), cadmium (100 micrometer), mercury (100 micrometer) or manganese (1 mM) treatment induced apoptotic phenomena like DNA fragmentation, chromatin condensation and caspase-3-like cysteine protease activation in MC3T3E1 osteoblasts. Concomitant treatment of antioxidant; N-acetyl-L-cysteine (NAC), reduced-form glutathione (GSH), or superoxide dismutase (SOD), prevented apoptosis induced by each of the transition metal ions. Catalase or dimethylsulfoxide (DMSO) has less potent inhibitory effect on the apoptosis, compared with NAC, GSH or SOD. In line with the results, nitroblue tetrazolium (NBT) stain shows that each of the transition metals is a potent source of free radicals in MC3T3E1 osteoblast. Our data show that oxidative damage is associated with the induction of apoptosis in MC3T3E1 osteoblasts following Se2+, Cd2+, Hg2+ or Mn2+ treatment.


MeSH Terms

Acetylcysteine
Apoptosis*
Cadmium
Catalase
Chromatin
Cysteine
Cysteine Proteases
Dimethyl Sulfoxide
DNA Fragmentation
Free Radicals
Glutathione
Ions
Manganese
Metabolism
Metals
Nitroblue Tetrazolium
Osteoblasts*
Reactive Oxygen Species
Selenium
Superoxide Dismutase
Acetylcysteine
Cadmium
Catalase
Chromatin
Cysteine
Cysteine Proteases
Dimethyl Sulfoxide
Free Radicals
Glutathione
Ions
Manganese
Metals
Nitroblue Tetrazolium
Reactive Oxygen Species
Selenium
Superoxide Dismutase
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