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.