Nuclear factor KB inactivation in the rat liver ameliorates short term total warm ischaemia/reperfusion injury

Suetsugu, H.; Limuro, Y.; Ueharo, T.; Nishio, T.; Harada, N.; Yoshida, M.; Hatano, E.; Son, G.; Fujimoto, J.; Yamaoka, Y.
June 2005
Gut;Jun2005, Vol. 54 Issue 6, p835
Academic Journal
Background: In hepatic ischaemia/reperfusion injury, activated liver macrophages (Kupffer cells) are dominantly regulated by a transcription factor, nuclear factor κB (NFκB), with respect to expression of inflammatory cytokines, acute phase response proteins, and cell adhesion molecules. Aims: We assessed whether inactivation of NF; in the liver could attenuate total hepatic warm ischaemia/reperfusion injury. Methods: We studied rats with hepatic overexpression of inhibitor κBα super-repressor (lκBα SR) caused by a transgene introduced using an adenoviral vector. Hepatic ischaemia/reperfusion injury was induced under warm conditions by total occlusion of hepatoduodenal ligament structures for 20 minutes, followed by reperfusion. Controls included uninfected and control virus (AdLacZ) infected rats. Results: lκBα SR was overexpressed in Kupffer cells as well as in hepatocytes, blocking nuclear translocation of NFκB (p65) into the nucleus after reperfusion. Gene transfection with IκBα SR, but not with LacZ, markedly attenuated ischaemia/reperfusion injury, suppressing inducible nitric oxide synthase and nitrotyrosine expression in the liver. Moreover, no remarkable hepatocyte apoptosis was detected under IκBα SR overexpression. Conclusions: Adenoviral transfer of the lκBα SR gene in the liver ameliorates short term warm ischaemia/ reperfusion injury, possibly through attenuation of hepatic macrophage activation.


Related Articles

  • Beneficial Effects of Follistatin in Hepatic Ischemia-Reperfusion Injuries in Rats. Kanamoto, Mami; Shimada, Mitsuo; Morine, Yuji; Yoshizumi, Tomoharu; Imura, Satoru; Ikegami, Toru; Mori, Hiroki; Arakawa, Yusuke // Digestive Diseases & Sciences;Apr2011, Vol. 56 Issue 4, p1075 

    Background: Ischemia-reperfusion injury has been demonstrated in a variety of clinical settings. The morbidity associated with liver transplantation and major hepatic resections is partly a result of ischemia-reperfusion injury. Follistatin, an activin-binding protein, binds to activins and...

  • HMGB1 in ischemic and non-ischemic liver after selective warm ischemia/reperfusion in rat. Liu, Anding; Dirsch, Olaf; Fang, Haoshu; Sun, Jian; Jin, Hao; Dong, Wei; Dahmen, Uta // Histochemistry & Cell Biology;May2011, Vol. 135 Issue 5, p443 

    High mobility group box 1 (HMGB1) acts as an early mediator in inflammation and organ injury. Ischemia reperfusion (I/R) injury induces HMGB1 translocation and expression in ischemic areas. However, it is unknown whether selective warm liver I/R injury also induces the expression of HMGB1 in...

  • Atorvastatin Protects against Ischemia-Reperfusion Injury in Fructose-Induced Insulin Resistant Rats. Prakash, Prem; Khanna, Vivek; Singh, Vishal; Jyoti, Anupam; Jain, Manish; Keshari, Ravi; Barthwal, Manoj; Dikshit, Madhu // Cardiovascular Drugs & Therapy;Aug2011, Vol. 25 Issue 4, p285 

    Purpose: High fructose (HFr) intake is known to cause insulin resistance syndrome (IRS), however its effect against acute coronary events remains elusive. The present study was undertaken to evaluate the effect of HFr (60%) diet on myocardial ischemia-reperfusion (MI-RP) injury and its...

  • l-Tetrahydropalmatine, an Active Component of Corydalis yanhusuo W.T. Wang, Protects against Myocardial Ischaemia-Reperfusion Injury in Rats. Yi Han; Wen Zhang; Yan Tang; Wenli Bai; Fan Yang; Liping Xie; Xiaozhen Li; Suming Zhou; Shiyang Pan; Qi Chen; Ferro, Albert; Yong Ji // PLoS ONE;Jun2012, Vol. 7 Issue 6, p1 

    l-Tetrahydropalmatine (l-THP) is an active ingredients of Corydalis yanhusuo W.T. Wang, which protects against acute global cerebral ischaemia-reperfusion injury. In this study, we show that l-THP is cardioprotective in myocardial ischaemiareperfusion injury and examined the mechanism. Rats were...

  • Upregulation of CaMKIIδ during ischaemia-reperfusion is associated with reperfusion-induced arrhythmias and mechanical dysfunction of the rat heart: involvement of sarcolemmal Ca2+-cycling proteins.  // Canadian Journal of Physiology & Pharmacology;Aug2012, Vol. 90 Issue 8, p1127 

    Although Ca2+/calmodulin-dependent protein kinase II delta (CaMKIIδ) has been implicated in development of different phenotypes of myocardial ischaemia-reperfusion injury, its involvement in arrhythmogenesis and cardiac stunning is not sufficiently elucidated. Moreover, the mechanisms by...

  • The Administration of Renoprotective Agents Extends Warm Ischemia in a Rat Model. Cohen, Jacob; Dorai, Thambi; Ding, Cheng; Batinic-Haberle, Ines; Grasso, Michael // Journal of Endourology;Mar2013, Vol. 27 Issue 3, p343 

    Background and Purpose: Extended warm ischemia time during partial nephrectomy leads to considerable renal injury. Using a rat model of renal ischemia, we examined the ability of a unique renoprotective cocktail to ameliorate warm ischemia-reperfusion injury and extend warm ischemia time....

  • Nucleolin protects the heart from ischaemia—reperfusion injury by up-regulating heat shock protein 32. Jiang, Bimei; Zhang, Bin; Liang, Pengfei; Chen, Guangwen; Zhou, Bin; Lv, Chunliu; Tu, Zizhi; Xiao, Xianzhong // Cardiovascular Research;Jul2013, Vol. 99 Issue 1, p92 

    Aims Nucleolin plays important roles in a variety of cellular processes. In this study, we aimed to investigate the role of nucleolin in cardiac ischaemia–reperfusion (I–R) injury. Methods and results We investigated the expression pattern of nucleolin in hearts subjected to...

  • Glutamine Does Not Protect Against Hepatic Warm Ischemia/Reperfusion Injury in Rats. Noh, Joonhwa; Behrends, Matthias; Choi, Soojinna; Bedolli, Melanie A.; Yardi, Jason; Hirose, Ryutaro; Niemann, Claus U. // Journal of Gastrointestinal Surgery;Feb2006, Vol. 10 Issue 2, p234 

    The administration of glutamine before experimental ischemia/reperfusion (I/R) has been shown to protect intestinal, pulmonary, and myocardial tissue by inducing heat shock proteins (HSP). However, it is not known whether glutamine is protective for all organs. We therefore tested whether...

  • Hydroxysafflor Yellow A Protects Against Cerebral Ischemia-Reperfusion Injury by Anti-apoptotic Effect Through PI3K/Akt/GSK3β Pathway in Rat. Chen, Lin; Xiang, Yanxiao; Kong, Lingjun; Zhang, Xiumei; Sun, Baozhu; Wei, Xinbing; Liu, Huiqing // Neurochemical Research;Nov2013, Vol. 38 Issue 11, p2268 

    Hydroxysafflor yellow A (HSYA) is the major active chemical component of the flower of the safflower plant, Carthamus tinctorius L. Previously, its neuroprotection against cerebral ischemia-reperfusion (I/R) injury was reported by anti-oxidant action and suppression of thrombin generation. Here,...


Read the Article


Sign out of this library

Other Topics