Nitroalkenes induce rat aortic smooth muscle cell apoptosis via activation of caspase-dependent pathways |
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Authors: | Xiaochun Tang Yanhong Guo Huarong Huang Lin Chang Kejie Yin Jifeng Zhang |
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Institution: | a Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, University of Michigan, Ann Arbor, MI 48109, USA b Department of Animal Biotechnology, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin Province, PR China |
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Abstract: | Nitroalkene derivatives of nitro-linoleic acid (LNO2) and nitro-oleic acid (OA-NO2) are nitrated unsaturated fatty acids that can be detected in healthy human plasma, red blood cells and urine. It has been shown that nitroalkenes have potent anti-inflammatory properties in multiple disease models. In the present study, we are the first to investigate the apoptotic effects of nitroalkenes in rat aortic smooth muscle cells (RASMCs). We observed that nitroalkenes induce RASMCs apoptosis in a dose-dependent manner. In addition, nitroalkenes stimulate extrinsic caspase-8 and intrinsic caspase-9 activity to trigger the caspase-3 apoptotic signaling cascade, resulting in RASMCs death. Furthermore, the pro-apoptotic protein, Bad was upregulated and antiapoptotic protein, Bcl-xl was downregulated during nitroalkene-induced apoptosis. These results demonstrate that nitroalkenes can induce RASMCs apoptosis via stimulation of caspase activity and the regulation of apoptotic protein expression levels. |
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Keywords: | Nitroalkene Caspase Apoptosis Rat aortic smooth muscle cells |
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