کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2775905 1152351 2008 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Poly (ADP) ribose synthetase inhibition in alveolar macrophages undergoing hypoxia and reoxygenation
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوشیمی بالینی
پیش نمایش صفحه اول مقاله
Poly (ADP) ribose synthetase inhibition in alveolar macrophages undergoing hypoxia and reoxygenation
چکیده انگلیسی

BackgroundInhibition of the nuclear enzyme poly ribose synthetase (PARS) protects against in vivo lung ischemia reperfusion injury (LIRI). The effectiveness of intratracheal treatment suggests that PARS inhibition may primarily modulate alveolar macrophage (AM) activation. These studies attempted to characterize the effects of PARS on AM activation in response to oxidative stress.MethodsPrimary cultures of AM were rendered hypoxic for 2 h and reoxygenated for up to 4 h. Cells were preincubated with INO-1001, a specific PARS inhibitor 1 h prior to hypoxia. Gel shift assays characterized nuclear factor kappa B (NFκB), and enzyme linked immunosorbent assay quantitated chemokine/cytokine protein secretion.ResultsHypoxia and reoxygenation resulted in an increase in the early nuclear translocation of NFκB, and an increase in the secretion of the cytokine tumor necrosis factor-alpha (TNF-α), chemokines macrophage inflammatory protein (MIP-1α), monocyte chemoattractant protein one (MCP-1) and cytokine induced neutrophil chemoattractant (CINC). Pretreatment of AM with INO-1001 decreased both the early translocation of NFκB and the production of TNF-α (p < 0.05) and MIP-1α p = 0.02, but did not affect CINC or MCP-1 production.ConclusionsThese findings indicate that PARS inhibition in the AM blunts their response to oxidative stress and may help explain the protective effects of intratracheal PARS inhibition in LIRI.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental and Molecular Pathology - Volume 84, Issue 2, April 2008, Pages 141–144
نویسندگان
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