GATA-3 transduces survival signals in osteoblasts through upregulation of bcl-xL gene expression

Ruei Ming Chen, Yi Ling Lin, Chih Wei Chou

研究成果: 雜誌貢獻文章同行評審

30 引文 斯高帕斯(Scopus)

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 stress-induced apoptotic insults. Such protection involved enhancement of Bcl-XL 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-XL 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-XL 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-XL expression and cell survival. Therefore, this study shows that GATA-3 plays critical roles in mediating survival signals in osteoblasts, possibly through upregulating bcl-XL gene expression.

原文英語
頁(從 - 到)2193-2204
頁數12
期刊Journal of Bone and Mineral Research
25
發行號10
DOIs
出版狀態已發佈 - 十月 2010

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

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