Cadmium induces apoptosis in primary rat osteoblasts through caspase and mitogen-activated protein kinase pathways.
10.4142/jvs.2015.16.3.297
- Author:
Hongyan ZHAO
1
;
Wei LIU
;
Yi WANG
;
Nannan DAI
;
Jianhong GU
;
Yan YUAN
;
Xuezhong LIU
;
Jianchun BIAN
;
Zong Ping LIU
Author Information
1. College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. liuzongping@yzu.edu.cn
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
apoptosis;
cadmium;
caspase;
mitogen-activated protein kinase;
osteoblasts
- MeSH:
Animals;
Apoptosis/*drug effects;
Cadmium/*toxicity;
Caspases/metabolism;
Environmental Pollutants/*toxicity;
Osteoblasts/*drug effects/metabolism;
Oxidative Stress/drug effects;
Rats;
Rats, Sprague-Dawley;
p38 Mitogen-Activated Protein Kinases/metabolism
- From:Journal of Veterinary Science
2015;16(3):297-306
- CountryRepublic of Korea
- Language:English
-
Abstract:
Exposure to cadmium (Cd) induces apoptosis in osteoblasts (OBs); however, little information is available regarding the specific mechanisms of Cd-induced primary rat OB apoptosis. In this study, Cd reduced cell viability, damaged cell membranes and induced apoptosis in OBs. We observed decreased mitochondrial transmembrane potentials, ultrastructure collapse, enhanced caspase-3 activity, and increased concentrations of cleaved PARP, cleaved caspase-9 and cleaved caspase-3 following Cd treatment. Cd also increased the phosphorylation of p38-mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases (ERK)1/2 and c-jun N-terminal kinase (JNK) in OBs. Pretreatment with the caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, ERK1/2 inhibitor (U0126), p38 inhibitor (SB203580) and JNK inhibitor (SP600125) abrogated Cd-induced cell apoptosis. Furthermore, Cd-treated OBs exhibited signs of oxidative stress protection, including increased antioxidant enzymes superoxide dismutase and glutathione reductase levels and decreased formation of reactive oxygen species. Taken together, the results of our study clarified that Cd has direct cytotoxic effects on OBs, which are mediated by caspase- and MAPK pathways in Cd-induced apoptosis of OBs.
