Examination of the ability of tumor necrosis factor-␣ (TNF) to activate both the p44/42 and p38 MAP kinase cascades in fully differentiated 3T3-L1 adipocytes indicated a rapid MEK1/2-dependent activation of p44/42 MAP kinase. Use of the MEK1/2 inhibitor PD98059 indicated that this pathway at least i
Amyloid precursor protein expression is induced by tumor necrosis factor α in 3T3-L1 adipocytes
✍ Scribed by Grit Sommer; Susan Kralisch; Jana Lipfert; Sebastian Weise; Kerstin Krause; Beate Jessnitzer; Ulrike Lössner; Matthias Blüher; Michael Stumvoll; Mathias Fasshauer
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 172 KB
- Volume
- 108
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Abstract
Amyloid precursor protein (APP) has been characterized as an adipocyte‐secreted protein that might contribute to obesity‐related insulin resistance, inflammation, and dementia. In the current study, regulation of APP by the proinflammatory and insulin resistance‐inducing cytokine tumor necrosis factor (TNF) α was determined in 3T3‐L1 adipocytes. Interestingly, APP protein synthesis and mRNA expression were significantly increased by TNFα in a time‐dependent manner with maximal induction observed after 24 h of treatment. Furthermore, TNFα induced APP mRNA expression dose‐dependently with maximal 6.4‐fold upregulation seen at 100 ng/ml effector. Moreover, inhibitor experiments suggested that TNFα‐induced APP expression was mediated by nuclear factor κ B. Taken together, we show for the first time a potent upregulation of APP by TNFα suggesting a potential role of this adipocyte‐secreted protein in TNFα‐induced insulin resistance and inflammatory disease. J. Cell. Biochem. 108: 1418–1422, 2009. © 2009 Wiley‐Liss, Inc.
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