Difference between revisions of "Garcia 2015 FASEB J"
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|title=GarcĂa JA, Volt H, Venegas C, Doerrier C, Escames G, LĂłpez LC, Acuña-Castroviejo D (2015) Disruption of the NF-ÎșB/NLRP3 connection by melatonin requires retinoid-related orphan receptor-α and blocks the septic response in mice. FASEB J [Epub ahead of print].  | |title=GarcĂa JA, Volt H, Venegas C, Doerrier C, Escames G, LĂłpez LC, Acuña-Castroviejo D (2015) Disruption of the NF-ÎșB/NLRP3 connection by melatonin requires retinoid-related orphan receptor-α and blocks the septic response in mice. FASEB J [Epub ahead of print]. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/26045547 PMID: 26045547] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/26045547 PMID: 26045547] | ||
|authors=Garcia JA, Volt H, Venegas C, Doerrier C, Escames G, Lopez LC, Acuna-Castroviejo D | |authors=Garcia JA, Volt H, Venegas C, Doerrier C, Escames G, Lopez LC, Acuna-Castroviejo D | ||
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{{Labeling | {{Labeling | ||
|area=Respiration | |area=Respiration, mtDNA;mt-genetics, Pharmacology;toxicology | ||
|organism=Mouse | |organism=Mouse | ||
|tissues=Heart | |tissues=Heart | ||
|preparations=Permeabilized tissue | |||
|diseases=Sepsis | |diseases=Sepsis | ||
|couplingstates=OXPHOS | |||
|substratestates=CI, CII, ROX | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional=Labels, [Epub ahead of print] | |additional=Labels, [Epub ahead of print] | ||
}} | }} |
Revision as of 09:18, 15 June 2015
GarcĂa JA, Volt H, Venegas C, Doerrier C, Escames G, LĂłpez LC, Acuña-Castroviejo D (2015) Disruption of the NF-ÎșB/NLRP3 connection by melatonin requires retinoid-related orphan receptor-α and blocks the septic response in mice. FASEB J [Epub ahead of print]. |
Garcia JA, Volt H, Venegas C, Doerrier C, Escames G, Lopez LC, Acuna-Castroviejo D (2015) FASEB J
Abstract: We determined the NF-ÎșB- and NOD-like receptor (NLR)P3-dependent molecular mechanisms involved in sepsis and evaluated the role of retinoid-related orphan receptor (ROR)-α in melatonin's anti-inflammatory actions. Western blot, RT-PCR, ELISA, and spectrophotometric analysis revealed that NF-ÎșB and NLRP3 closely interact, leading to proinflammatory and pro-oxidant status in heart tissue of septic C57BL/6J mice. Moreover, mitochondrial oxygen consumption was reduced by 80% in septic mice. In vivo and in vitro analysis showed that melatonin administration blunts NF-ÎșB transcriptional activity through a sirtuin1-dependent NF-ÎșB deacetylation in septic mice. Melatonin also decreased NF-ÎșB-dependent proinflammatory response and restored redox balance and mitochondrial homeostasis, thus inhibiting the NLRP3 inflammasome. In an important finding, the inhibition of NF-ÎșB by melatonin, but not that of NLRP3, was blunted in RORαsg/sg mice, indicating that functional RORα transcription factor is necessary for the initiation of the innate immune response against inflammation. Our results are evidence of the NF-ÎșB/NLRP3 connection during sepsis and identify NLRP3 as a novel molecular target for melatonin. The multiple molecular targets of melatonin in this study explain its potent anti-inflammatory efficacy against systemic innate immune activation and herald a promising therapeutic application for melatonin in the treatment of sepsis. âą Keywords: Bmal1, Inflammasome, Innate immunity, Oxidative stress, Sirtuin-1
âą O2k-Network Lab: AT Innsbruck OROBOROS, ES Granada Acuna-Castroviejo D
Labels: MiParea: Respiration, mtDNA;mt-genetics, Pharmacology;toxicology
Pathology: Sepsis
Organism: Mouse Tissue;cell: Heart Preparation: Permeabilized tissue
Coupling state: OXPHOS
HRR: Oxygraph-2k
Labels, [Epub ahead of print]