Lodygin, Dmitri

[["dc.bibliographiccitation.firstpage","46862"],["dc.bibliographiccitation.issue","30"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","46870"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Winter, Markus"],["dc.contributor.author","Lodygin, Dmitri"],["dc.contributor.author","Verdoodt, Berlinda"],["dc.contributor.author","Hermeking, Heiko"],["dc.date.accessioned","2018-11-07T10:11:28Z"],["dc.date.available","2018-11-07T10:11:28Z"],["dc.date.issued","2016"],["dc.description.abstract","The p53-inducible cell cycle regulator 14-3-3 sigma exhibits tumor suppressive functions and is highly expressed in differentiating layers of the epidermis and hair follicles. 14-3-3 sigma/SFN/stratifin is frequently silenced in human epithelial cancers, and experimental down-regulation of 14-3-3 sigma expression immortalizes primary human keratinocytes. In the repeated-epilation (ER) mouse model, a heterozygous nonsense mutation of 14-3-3 sigma causes repeated hair-loss, hyper-proliferative epidermis, and spontaneous development of papillomas and squamous cell carcinomas in aging mice. Therefore, loss of 14-3-3 sigma function might contribute to epithelial tumor development. Here, we generated mice with loxP sites surrounding the single 14-3-3 sigma exon which allowed Cre-mediated deletion of the gene. 14-3-3 sigma-deficient mice are viable, but demonstrate a permanently disheveled fur. However, histological analyses of the skin did not reveal obvious defects in the hair follicles or the epidermis. Deletion of 14-3-3 sigma did not enhance spontaneous epidermal tumor development, whereas it increased the frequency and size of DMBA/TPA-induced papillomas. In conclusion, 14-3-3 sigma is dispensable for normal epidermal homeostasis but critical for suppression of chemically-induced skin carcinogenesis. In addition, these results suggest that the ER mutation of 14-3-3 sigma is not equivalent to loss of 14-3-3 sigma, but may represent a gain-of-function variant, which does not reflect the organismal function of wild-type 14-3-3 sigma."],["dc.identifier.doi","10.18632/oncotarget.10478"],["dc.identifier.isi","000385413000004"],["dc.identifier.pmid","27409835"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14135"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40051"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Impact Journals Llc"],["dc.relation.issn","1949-2553"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Deletion of 14-3-3 sigma sensitizes mice to DMBA/TPA-induced papillomatosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1930"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","1943"],["dc.bibliographiccitation.volume","133"],["dc.contributor.author","Cordiglieri, Chiara"],["dc.contributor.author","Odoardi, Francesca"],["dc.contributor.author","Zhang, B. O."],["dc.contributor.author","Nebel, Merle"],["dc.contributor.author","Kawakami, Naoto"],["dc.contributor.author","Klinkert, Wolfgang E. F."],["dc.contributor.author","Lodygin, Dimtri"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Breunig, Esther"],["dc.contributor.author","Schild, Detlev"],["dc.contributor.author","Ulaganathan, Vijay Kumar"],["dc.contributor.author","Dornmair, Klaus"],["dc.contributor.author","Dammermann, Werner"],["dc.contributor.author","Potter, Barry V. L."],["dc.contributor.author","Guse, Andreas H."],["dc.contributor.author","Fluegel, Alexander"],["dc.date.accessioned","2018-11-07T08:41:30Z"],["dc.date.available","2018-11-07T08:41:30Z"],["dc.date.issued","2010"],["dc.description.abstract","Nicotinic acid adenine dinucleotide phosphate represents a newly identified second messenger in T cells involved in antigen receptor-mediated calcium signalling. Its function in vivo is, however, unknown due to the lack of biocompatible inhibitors. Using a recently developed inhibitor, we explored the role of nicotinic acid adenine dinucleotide phosphate in autoreactive effector T cells during experimental autoimmune encephalomyelitis, the animal model for multiple sclerosis. We provide in vitro and in vivo evidence that calcium signalling controlled by nicotinic acid adenine dinucleotide phosphate is relevant for the pathogenic potential of autoimmune effector T cells. Live two photon imaging and molecular analyses revealed that nicotinic acid adenine dinucleotide phosphate signalling regulates T cell motility and re-activation upon arrival in the nervous tissues. Treatment with the nicotinic acid adenine dinucleotide phosphate inhibitor significantly reduced both the number of stable arrests of effector T cells and their invasive capacity. The levels of pro-inflammatory cytokines interferon-gamma and interleukin-17 were strongly diminished. Consecutively, the clinical symptoms of experimental autoimmune encephalomyelitis were ameliorated. In vitro, antigen-triggered T cell proliferation and cytokine production were evenly suppressed. These inhibitory effects were reversible: after wash-out of the nicotinic acid adenine dinucleotide phosphate antagonist, the effector T cells fully regained their functions. The nicotinic acid derivative BZ194 induced this transient state of non-responsiveness specifically in post-activated effector T cells. Naive and long-lived memory T cells, which express lower levels of the putative nicotinic acid adenine dinucleotide phosphate receptor, type 1 ryanodine receptor, were not targeted. T cell priming and recall responses in vivo were not reduced. These data indicate that the nicotinic acid adenine dinucleotide phosphate/calcium signalling pathway is essential for the recruitment and the activation of autoaggressive effector T cells within their target organ. Interference with this signalling pathway suppresses the formation of autoimmune inflammatory lesions and thus might qualify as a novel strategy for the treatment of T cell mediated autoimmune diseases."],["dc.identifier.doi","10.1093/brain/awq135"],["dc.identifier.isi","000279473900008"],["dc.identifier.pmid","20519328"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6202"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19486"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0006-8950"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Nicotinic acid adenine dinucleotide phosphate-mediated calcium signalling in effector T cells regulates autoimmunity of the central nervous system"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]