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学科主题: 临床医学
题名:
Phenylarsine oxide inhibited beta-adrenergic receptor-mediated IL-6 secretion: Inhibition of cAMP accumulation and CREB activation in cardiac fibroblasts
作者: Du, Jian-Hai; Guan, Tong-Ju; Zhang, Hui; Xiao, Han; Han, Qi-De; Zhang, You-Yi
关键词: phenylarsine oxide ; interleukin-6 ; beta-adrenergic receptors ; cardiac fibroblasts
刊名: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
发表日期: 2007-01-19
DOI: 10.1016/j.bbrc.2006.11.082
卷: 352, 期:3, 页:744-749
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Biophysics
研究领域[WOS]: Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]: CONGESTIVE-HEART-FAILURE ; TYROSINE-PHOSPHATASE ; KAPPA-B ; CELLS ; PHOSPHORYLATION ; EXPRESSION ; INTERLEUKIN-6 ; PATHWAY ; BINDING ; KINASE
英文摘要:

As we previously reported, cAMP and p38 MAPK instead of protein kinase A were involved in beta-adrenergic receptor (beta-AR)-mediated interleukin-6 (IL-6) production in mouse cardiac fibroblasts. Besides kinases, phosphatases may also be involved in IL-6 gene regulation. To study the role of protein tyrosine phosphatases (PTPs) in beta-AR-mediated IL-6 production, we selected the most widely used PTP inhibitor, phenylarsine oxide (PAO). We found that PAO dose-dependently inhibited the IL-6 release in response to beta-AR agonist isoproterenol (ISO) in mouse cardiac fibroblasts. This effect was probably due to the inhibition of PTPs, resulting in increased tyrosine phosphorylation, since genistein, an inhibitor of protein tyrosine kinases further potentiated ISO-induced IL-6 production and could partially reverse the inhibitory effect of PAO. PAO also significantly inhibited the IL-6 production by forskolin, an adenylyl cyclase (AC) activator. Furthermore, PAO dose-dependently inhibited the increased cAMP accumulation by either ISO or forskolin and suppressed the phosphorylation of CREB, an important transcriptional factor for IL-6 gene expression. But PAO did not affect the activation of p38 MAPK by ISO. Although PAO was also reported to inhibit NADPH oxidase, the inhibition of NADPH oxidase by its specific inhibitor, diphenylene iodonium (DPI) could not suppress beta-AR-mediated IL-6 production, suggesting that NADPH oxidase may not contribute to the inhibitory effect of PAO on IL-6 production. To our knowledge, this is the first report that PAO can inhibit ISO-induced IL-6 expression and CREB phosphorylation, demonstrating that PTPs may negatively regulate beta-AR-mediated IL-6 production. This study may also further our understanding of beta-AR signaling and provide potential therapeutic targets for the treatment of heart diseases. (c) 2006 Elsevier Inc. All rights reserved.

语种: 英语
WOS记录号: WOS:000243147000027
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59668
Appears in Collections:北京大学第三临床医学院_心血管内科_期刊论文

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作者单位: 1.Peking Univ, Hosp 3, Inst Vasc Med, Beijing 100083, Peoples R China
2.Key Lab Cardiovasc Sci, Minist Educ, Beijing 100083, Peoples R China
3.Lanzhou Univ, Sch Basic Med Sci, Inst Pathol, Lanzhou 730000, Peoples R China

Recommended Citation:
Du, Jian-Hai,Guan, Tong-Ju,Zhang, Hui,et al. Phenylarsine oxide inhibited beta-adrenergic receptor-mediated IL-6 secretion: Inhibition of cAMP accumulation and CREB activation in cardiac fibroblasts[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2007,352(3):744-749.
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