4.6 Article

Involvement of H-Ras and reactive oxygen species in proinflammatory cytokine-induced matrix metalloproteinase-13 expression in human articular chondrocytes

期刊

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 507, 期 2, 页码 350-355

出版社

ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2010.12.032

关键词

Cartilage; Ras; RNA interference; Manumycin; Diphenyleneiodonium; Antioxidants

资金

  1. Canadian Institutes of Health Research (CIHR) [MOP-57848]
  2. Morehouse School of Medicine

向作者/读者索取更多资源

Proinflammatory cytokines such as interleukin-1 beta (11,10) and tumor necrosis factor alpha (TNF-alpha) enhance degradation of cartilage-specific, type II collagen by matrix metalloproteinase-13 (MMP-13). We investigated the previously unknown role of H-Ras and reactive oxygen species (ROS) in the cytokine induction of MMP-13 gene expression in human articular chondrocytes by using pharmacological inhibitors, RNA interference (RNAi) and antioxidants. Manumycin A, an inhibitor of H-Ras farnesylation by famesyltransferase, suppressed IL-1 beta- and TNF-alpha-induced MMP-13 mRNA and protein expression. Small interfering RNA (siRNA)-mediated H-Ras silencing down-regulated MMP-13 mRNA and protein induction by IL-beta and TNF-alpha. Nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase/NOX) inhibitor, diphenyleneiodonium (DPI) suppressed cytokine-induced MMP-13 expression and superoxide production. Apocynin, another NOX inhibitor, also diminished MMP-13 induction. Deoxyglucose an antimetabolite of glucose metabolism reduced MMP-13 increase. Role of NOX-mediated ROS production was reaffirmed by the observation that the antioxidants, trolox, nordihydroguaiaretic acid (NDGA), quercetin and resveratrol downregulated cytokine-induced MMP-13 mRNA and protein expression. These results provide strong pharmacological and genetic evidence for the implication of H-Ras and NADPH oxidase-generated superoxide production in MMP-beta gene regulation by IL-beta and TNF-alpha. These proteins could be potentially targeted for therapeutic inhibition of MMP-13-driven cartilage erosion by using H-Ras and NOX inhibitors and antioxidants. (C) 2011 Elsevier Inc. All rights reserved.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
Article Biochemistry & Molecular Biology

Activation of the TGF-81/EMT signaling pathway by claudin-1 overexpression reduces doxorubicin sensitivity in small cell lung cancer SBC-3 cells

Yuri Nagaoka, Kotone Oshiro, Yuta Yoshino, Toshiyuki Matsunaga, Satoshi Endo, Akira Ikari

Summary: This study investigated the effect of intercellular adhesion molecule CLDN1 on the anticancer drug sensitivity of small-cell lung cancer (SCLC) cells. It was found that overexpression of CLDN1 decreased the sensitivity of SCLC cells to anticancer drugs and enhanced their migratory capacity through the activation of the TGF-81/EMT signaling pathway. Treatment with EMT inhibitors showed potential in overcoming the reduced sensitivity to anticancer drugs in CLDN1-overexpressing SCLC cells.

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS (2024)