期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 89, 期 -, 页码 158-169出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2015.07.154
关键词
Innate immunity; Inflammation; NOD; Insulin resistance; Mitochondrial function; Free radicals
资金
- Science and Engineering Research Board, New Delhi, India [SERC-0315/2010]
- CSIR, New Delhi, India [BSC0102, CSC-0111]
- University Grant Commission, New Delhi
- Indian Council of Medical Research, New Delhi
- CSIR Network project
Nucleotide binding oligomerization domain protein-2 (NOD2) activation in skeletal muscle cells has been associated with insulin resistance, but the underlying mechanisms are not yet clear. Here we demonstrate the implication of oxidative stress in the development of mitochondrial dysfunction and insulin resistance in response to NOD2 activation in skeletal muscle cells. Treatment with the selective NOD2 ligand muramyl dipeptide (MDP) increased mitochondrial reactive oxygen species (ROS) generation in L6 myotubes. MDP-induced ROS production was associated with increased levels of protein carbonyls and reduction in citrate synthase activity, cellular ATP level, and mitochondrial membrane potential, as well as altered expression of genes involved in mitochondrial function and metabolism. Antioxidant treatment attenuated MDP-induced ROS production and restored mitochondrial functions. In addition, the presence of antioxidant prevented NOD2-mediated activation of MAPK kinases and the inflammatory response. This was associated with reduced serine phosphorylation of insulin receptor substrate-1 (IRS-1) and improved insulin-stimulated tyrosine phosphorylation of IRS-1 and downstream activation of Aid phosphorylation. These data indicate that oxidative stress plays a role in NOD2 activation-induced inflammatory response and that MDP-induced oxidative stress correlates with impairment of mitochondrial functions and induction of insulin resistance in skeletal muscle cells. (C) 2015 Elsevier Inc. All rights reserved
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