RRC ID 68015
著者 Hinoi E, Takarada T, Tsuchihashi Y, Fujimori S, Moriguchi N, Wang L, Uno K, Yoneda Y.
タイトル A molecular mechanism of pyruvate protection against cytotoxicity of reactive oxygen species in osteoblasts.
ジャーナル Mol Pharmacol
Abstract We demonstrated previously that exogenous pyruvate has a protective action against cell death by hydrogen peroxide in cultured osteoblasts through a mechanism associated with its antioxidative property. In the present study, we have evaluated possible participation of monocarboxylate transporters (MCTs) responsible for the bidirectional membrane transport of pyruvate in the cytoprotective property in osteoblasts. Expression of the MCT2 isoform was found in cultured rat calvarial osteoblasts and in osteoblasts located on mouse tibia at both mRNA and protein levels. The accumulation of [14C]pyruvate occurred in a temperature- and pH-dependent manner in osteoblasts cultured for 7 days with high sensitivity to a specific MCT inhibitor, whereas pyruvate was released into extracellular spaces from cultured osteoblasts in a fashion sensitive to the MCT inhibitor. Transient overexpression of the MCT2 isoform led to reduced vulnerability to the cytotoxicity of hydrogen peroxide with an increased activity of [14C]pyruvate accumulation in murine osteoblastic MC3T3-E1 cells. Ovariectomy significantly decreased the content of pyruvate in femoral bone marrows in mice in vivo, whereas daily i.p. administration of pyruvate at 0.25 g/kg significantly prevented alterations of several histomorphometric parameters as well as cancellous bone loss in femurs by ovariectomy on 28 days after the operation. These results suggest that MCTs may be functionally expressed by osteoblasts to play a pivotal role in mechanisms related to the cytoprotective property of pyruvate.
巻・号 70(3)
ページ 925-35
公開日 2006-9-1
DOI 10.1124/mol.106.024398
PII mol.106.024398
PMID 16766717
MeSH Animals Bone Resorption Carbon Radioisotopes Cell Death / drug effects Cell Survival / drug effects Cells, Cultured Chondrocytes / drug effects Culture Media, Conditioned Female Gene Expression Profiling Gene Expression Regulation / drug effects Hydrogen Peroxide / metabolism* Hydrogen Peroxide / pharmacology Mice Models, Biological Monocarboxylic Acid Transporters / metabolism Osteoblasts / cytology* Osteoblasts / drug effects Osteoblasts / metabolism Ovariectomy Pyruvates / metabolism* RNA, Messenger / genetics RNA, Messenger / metabolism Rats Rats, Wistar Vitamin K 3 / pharmacology
IF 3.664
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126)