RGD Reference Report - Targeting of nicotinamide phosphoribosyltransferase enzymatic activity ameliorates lung damage induced by ischemia/reperfusion in rats. - Rat Genome Database

RGD Reference Report - Targeting of nicotinamide phosphoribosyltransferase enzymatic activity ameliorates lung damage induced by ischemia/reperfusion in rats. - Rat Genome Database

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General

Targeting of nicotinamide phosphoribosyltransferase enzymatic activity ameliorates lung damage induced by ischemia/reperfusion in rats.
Authors:	Wu, Geng-Chin Liao, Wen-I Wu, Shu-Yu Pao, Hsin-Ping Tang, Shih-En Li, Min-Hui Huang, Kun-Lun Chu, Shi-Jye
Citation:	Wu GC, etal., Respir Res. 2017 Apr 24;18(1):71. doi: 10.1186/s12931-017-0557-2.
RGD ID:	13781881
Pubmed:	PMID:28438162 (View Abstract at PubMed)
PMCID:	PMC5404693 (View Article at PubMed Central)
DOI:	DOI:10.1186/s12931-017-0557-2 (Journal Full-text)
BACKGROUND: Emerging evidence reveals that nicotinamide phosphoribosyltransferase (NAMPT) has a significant role in the pathophysiology of the inflammatory process. NAMPT inhibition has a beneficial effect in the treatment of a variety of inflammatory diseases. However, it remains unclear whether NAMPT inhibition has an impact on ischemia-reperfusion (I/R)-induced acute lung injury. In this study, we examined whether NAMPT inhibition provided protection against I/R lung injury in rats. METHODS: Isolated perfused rat lungs were subjected to 40 min of ischemia followed by 60 min of reperfusion. The rats were randomly allotted to the control, control¿+¿FK866 (NAMPT inhibitor, 10 mg/kg), I/R, or I/R¿+¿FK866 groups (n¿=¿6 per group). The effects of FK866 on human alveolar epithelial cells exposed to hypoxia-reoxygenation (H/R) were also investigated. RESULTS: Treatment with FK866 significantly attenuated the increases in lung edema, pulmonary arterial pressure, lung injury scores, and TNF-α, CINC-1, and IL-6 concentrations in bronchoalveolar lavage fluid in the I/R group. Malondialdehyde levels, carbonyl contents and MPO-positive cells in lung tissue were also significantly reduced by FK866. Additionally, FK866 mitigated I/R-stimulated degradation of IκB-α, nuclear translocation of NF-κB, Akt phosphorylation, activation of mitogen-activated protein kinase, and downregulated MKP-1 activity in the injured lung tissue. Furthermore, FK866 increased Bcl-2 and decreased caspase-3 activity in the I/R rat lungs. Comparably, the in vitro experiments showed that FK866 also inhibited IL-8 production and NF-κB activation in human alveolar epithelial cells exposed to H/R. CONCLUSIONS: Our findings suggest that NAMPT inhibition may be a novel therapeutic approach for I/R-induced lung injury. The protective effects involve the suppression of multiple signal pathways.

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Biological Process

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
regulation of lung blood pressure		IMP		13781881		RGD

Objects Annotated

Genes (Rattus norvegicus)

Nampt (nicotinamide phosphoribosyltransferase)

Additional Information