title: Systemic activation of NF-κB driven luciferase activity in transgenic mice fed advanced glycation end products modified albumin.
abstract: Advanced glycation end products (AGEs) are stable end products of the Maillard reaction and accumulate with progressing ageing and degenerative diseases. Significant amounts of AGE-modified peptides are also consumed with processed food. AGEs bind to specific receptors, especially the receptor of AGEs (RAGE). Activation of RAGE then evokes intracellular signalling, finally resulting in the activation of the NF-κB transcription factor and therefore a proinflammatory state. We here analysed, whether NF-κB is activated in short term upon feeding an AGE-modified protein in-vivo. Transgenic mice expressing firefly luciferase under the control of an NF-κB responsive promoter were intraperitoneally injected or fed with AGE-modified- or control albumin and luciferase expression was analysed by in-vivo imaging and by in-vitro by determination of luciferase enzyme activity in heart, lung, gut, spleen, liver and kidney. In all organs, an activation of the luciferase reporter gene was observed in response to AGE-BSA feeding, however with different intensity and timing. The gut exhibited highest luciferase activity and this activity peaked 6-8 h post AGE-feeding. In heart and kidney, luciferase activity increased for up to 12 h post feeding. All other organs tested, exhibited highest activity at 10 h after AGE-consumption. Altogether, these data demonstrate that feeding AGE-modified protein resulted in a transient and systemic activation of the NF-κB reporter.
authors.affiliation: Department of Cardiac Surgery, Middle German Heart Centre, University Hospital Halle (Saale), Ernst Grube Str. 40, D-06120, Halle Saale, Germany. norbert.nass@med.ovgu.de.|Institute of Pathology, Otto von Guericke University Magdeburg, Leipziger Str. 44, D- 39120, Magdeburg, Germany. norbert.nass@med.ovgu.de.
authors.forename: Norbert
authors.identifier: 0000-0003-2563-0386
authors.initials: N
authors.lastname: Nass
authors.affiliation: Department of Cardiac Surgery, Middle German Heart Centre, University Hospital Halle (Saale), Ernst Grube Str. 40, D-06120, Halle Saale, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Bayreuther
authors.affiliation: Department of Cardiac Surgery, Middle German Heart Centre, University Hospital Halle (Saale), Ernst Grube Str. 40, D-06120, Halle Saale, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Simm
mesh_terms: D000418:Albumins / Q000494:pharmacology*; D000818:Animals; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*; D019076:Transgenes
chemical_list: C000593873:Ager protein, mouse; D000418:Albumins; D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D008156:Luciferases
keywords: Advanced glycation end products; Luciferase; NF-κB; RAGE