title: V-PYRRO/NO downregulates mRNA expression levels of leukotriene C4 synthase during hepatic ischemia reperfusion injury in rats via inhibition of the nuclear factor-κB activation pathway.
abstract: The aim of the present study was to explore the mechanism underlying the effects of a selective liver nitric oxide (NO) donor, O2-vinyl1-(pyrrolidin-1-yl)-diazen-1-ium-1,2-diolate (V-PYRRO/NO), on the gene expression of leukotriene C4 synthase (LTC4S) during hepatic ischemia/reperfusion (I/R). Adult male Sprague-Dawley rats were divided into 3 groups: Sham (control), I/R and V-PYRRO/NO + I/R groups. The liver was subjected to 1 h of partial hepatic ischemia followed by 5 h of reperfusion, saline or V-PYRRO/NO (1.06 µmol/kg/h) administered intravenously. The mRNA expression levels of LTC4S in rat liver tissue were examined by the reverse transcription-polymerase chain reaction method, the protein expression levels of nuclear factor-κB (NF-κB) p65, p50 and IκBα in liver cell lysates and nuclear extracts were detected by western blot analysis. Hepatic mRNA expression of LTC4S was lower in V-PYRRO/NO + I/R group compared to the I/R group. In addition, the protein expression levels of NF-κB p65 and p50 in the nucleus extract were lower in the V-PYRRO/NO + I/R group when compared with the I/R group. However, the IκBα protein in the 3 groups was not changed. Immunohistochemistry staining revealed that the I/R liver exhibited strong cytoplasmic and nuclear staining for NF-κB p65; however, the V-PYRRO/NO + I/R group liver presented slight cytoplasmic and nuclear staining. In conclusion, V-PYRRO/NO may downregulate LTC4S mRNA expression by inhibiting NF-κB activation independent of IκBα during hepatic I/R injury.
authors: Department of Physiology, College of Medicine, Nanchang University, Nanchang, Jiangxi 330006, P.R. China; Department of Medical Experimental Teaching, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors: Feng-Fang
authors: FF
authors: Hong
authors: Institute of Cancer Research, Jiangxi Academy of Medical Science, Nanchang, Jiangxi 330006, P.R. China.
authors: Yi-Fan
authors: YF
authors: Wang
authors: Department of Physiology, College of Medicine, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors: Hui
authors: H
authors: Liu
authors: Fuzhou Medical College, Nanchang University, Fuzhou 344000, P.R. China.
authors: Mei-Wen
authors: MW
authors: Yang
authors: Department of Physiology, College of Medicine, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors: Shu-Long
authors: SL
authors: Yang
keywords: O2-vinyl1-(pyrrolidin-1-yl)- diazen-1-ium-1,2-diolate; ischemia reperfusion injury; leukotriene C4 synthase; liver; nitric oxide donor; nuclear factor-κB