Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10759313 | Biochemical and Biophysical Research Communications | 2013 | 6 Pages |
Abstract
We investigated whether arginase inhibition suppressed interleukin (IL)-1β-stimulated proliferation in vascular smooth muscle cells (VSMCs) and the possible mechanisms involved. IL-1β stimulation increased VSMC proliferation, while the arginase inhibitor BEC and transfection of the antisense (AS) oligonucleotide against arginase I decreased VSMC proliferation and was associated with increased protein content of the cell cycle regulator p21Waf1/Cip1. IL-1β incubation induced inducible nitric oxide synthase (iNOS) mRNA expression and protein levels in a dose-dependent manner, but did not affect arginase I and II expression. Consistent with this data, IL-1β stimulation resulted in increase in NO production that was significantly augmented by arginase inhibition. The specific iNOS inhibitor 1400W abolished IL-1β-mediated NO production and further accentuated IL-1β-stimulated cell proliferation. Incubation with NO donors GSNO and DETA/NO in the presence of IL-1β abolished VSMCs proliferation and increased p21Waf1/Cip1 protein content. Furthermore, incubation with the cGMP analogue 8-Br-cGMP prevented IL-1β-induced VSMCs proliferation. In conclusion, arginase inhibition augmented iNOS-dependent NO production that resulted in suppression of IL-1β-induced VSMCs proliferation in a cGMP-dependent manner.
Keywords
DMEMdiethylenetriamine NONOateDETA NONOateRASMCODQVSMC8-Br-cGMPS-nitrosoglutathioneGSNOnNOSIL-1βeNOSBECcGMPRT-PCRiNOS1400WDulbecco’s modified Eagle mediumArginaseAntisenseInterleukin-1βProliferationRat aortic smooth muscle cellVascular smooth muscle cellsinducible nitric oxide synthaseendothelial nitric oxide synthaseneuronal nitric oxide synthasecyclic guanosine monophosphatereverse transcription polymerase chain reaction
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Authors
Jeongyeon Yoon, Sungwoo Ryoo,