GATA-3 Transduces Survival Signals in Osteoblasts Through Upregulation of bcl-xL Gene Expression

被引:37
作者
Chen, Ruei-Ming [1 ,2 ,3 ]
Lin, Yi-Ling [2 ,3 ]
Chou, Chih-Wei [1 ]
机构
[1] Taipei Med Univ, Grad Inst Med Sci, Coll Med, Taipei 110, Taiwan
[2] Taipei Med Univ, Wan Fang Med Ctr, Cell Physiol & Mol Image Res Ctr, Taipei, Taiwan
[3] Taipei Med Univ, Wan Fang Med Ctr, Dept Anesthesiol, Taipei, Taiwan
关键词
GATA-3; OSTEOBLASTS; NO PRECONDITIONING; OXIDATIVE STRESS; APOPTOSIS; BCL-X-L; OXIDE PROTECTS OSTEOBLASTS; INDUCED APOPTOTIC INSULTS; BCL-X-L; NITRIC-OXIDE; TRANSCRIPTION FACTORS; SODIUM-NITROPRUSSIDE; CELL; BAX; BONE; ACTIVATION;
D O I
10.1002/jbmr.121
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
GATA-3, a transcription factor, participates in regulating cell development, proliferation, and death. This study was aimed at evaluating the roles of GATA-3 in protecting osteoblasts against oxidative stress-induced apoptotic insults and their possible mechanisms. Pretreatment with nitric oxide (NO) for 24 hours protected osteoblasts, prepared from neonatal rat calvaria, against oxidative stressinduced apoptotic insults. Such protection involved enhancement of Bcl-X-L messenger (m) RNA and protein syntheses and the translocation of this antiapoptotic protein from the cytoplasm to mitochondria. GATA-3 was detected in rat osteoblasts, and GATA-3-specific DNA-binding elements exist in the promoter region of the bcl-x(L) gene. NO preconditioning attenuated oxidative stress-caused suppression of GATA-3 mRNA and protein synthesis and the translocation of this transcription factor from the cytoplasm to nuclei. Application of GATA-3 small interfering (si) RNA into osteoblasts decreased the levels of this transcription factor and simultaneously inhibited Bcl-X-L mRNA synthesis. Pretreatment with NO lowered the oxidative stress-caused alteration in the binding of GATA-3 to its specific DNA motifs. Oxidative stress-inhibited Runx2 mRNA expression, but NO preconditioning decreased such inhibition. NO pretreatment time-dependently enhanced the association of GATA-3 with Runx2. Knocking down the translation of GATA-3 using RNA interference significantly decreased the protection of NO preconditioning against oxidative stress-induced alterations of cell morphologies, DNA fragmentation, and cell apoptosis. In comparison, overexpression of GATA-3 could promote NO preconditioning- involved Bcl-X-L expression and cell survival. Therefore, this study shows that GATA-3 plays critical roles in mediating survival signals in osteoblasts, possibly through upregulating bcl-x(L) gene expression. (C) 2010 American Society for Bone and Mineral Research.
引用
收藏
页码:2193 / 2204
页数:12
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