title: Colloidal carbon stimulation of Kupffer cells triggers Nrf2 activation in the isolated perfused rat liver.
abstract: Activation of transcription factor Nrf2 was investigated in the isolated perfused rat liver infused with 0.5 mg of colloidal carbon (CC)/ml for 5-15 min to stimulated Kupffer cell function. Infusion of CC enhanced liver O(2) consumption over basal levels, with a time-dependent increase in CC-induced O(2) uptake, at constant rates of CC phagocytosis by Kupffer cells, as assessed histologically, and adequate viability conditions of the livers, as shown by the marginal (0.34 %) total sinusoidal lactate dehydrogenase (LDH) efflux over intrahepatic LDH activity. Under these conditions, cytosolic protein levels of Nrf2 (Western blot) and inhibitor of Nrf2 Keap1 progressively declined by CC infusion, those of nuclear Nrf2 increased, leading to enhancement in the nuclear/cytosolic Nrf2 ratios. It is concluded that the respiratory burst of CC-stimulated Kupffer cells triggers Nrf2 activation in the perfused liver, a response that may afford cellular protection under pro-oxidant conditions underlying Kupffer cell stimulation.
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Núñez
authors.forename: Romina
authors.initials: R
authors.lastname: Vargas
authors.forename: Iván
authors.initials: I
authors.lastname: Castillo
authors.forename: Luis A
authors.initials: LA
authors.lastname: Videla
mesh_terms: D000818:Animals; D002244:Carbon / Q000494:pharmacology*; D003102:Colloids; D003600:Cytosol / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins; D000072019:Kelch-Like ECH-Associated Protein 1; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D009924:Organ Culture Techniques; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D010587:Phagocytosis / Q000187:drug effects; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D003102:Colloids; D047908:Intracellular Signaling Peptides and Proteins; C486610:KEAP1 protein, rat; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D011506:Proteins; D017382:Reactive Oxygen Species; D002244:Carbon; D007770:L-Lactate Dehydrogenase