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1.
Nat Commun ; 13(1): 941, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-35177595

RESUMO

During development, pseudostratified epithelia undergo large scale morphogenetic events associated with increased mechanical stress. Using a variety of genetic and imaging approaches, we uncover that in the mouse E6.5 epiblast, where apical tension is highest, ASPP2 safeguards tissue integrity. It achieves this by preventing the most apical daughter cells from delaminating apically following division events. In this context, ASPP2 maintains the integrity and organisation of the filamentous actin cytoskeleton at apical junctions. ASPP2 is also essential during gastrulation in the primitive streak, in somites and in the head fold region, suggesting that it is required across a wide range of pseudostratified epithelia during morphogenetic events that are accompanied by intense tissue remodelling. Finally, our study also suggests that the interaction between ASPP2 and PP1 is essential to the tumour suppressor function of ASPP2, which may be particularly relevant in the context of tissues that are subject to increased mechanical stress.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Epitélio/crescimento & desenvolvimento , Morfogênese , Proteínas Supressoras de Tumor/metabolismo , Citoesqueleto de Actina/metabolismo , Animais , Células CACO-2 , Polaridade Celular , Cães , Técnicas de Cultura Embrionária , Embrião de Mamíferos , Epitélio/metabolismo , Feminino , Gastrulação , Camadas Germinativas , Humanos , Células Madin Darby de Rim Canino , Camundongos , Camundongos Transgênicos , Mutação , Linha Primitiva , Receptores de Neuropeptídeo Y/metabolismo , Estresse Mecânico , Junções Íntimas/metabolismo , Proteínas Supressoras de Tumor/genética
2.
Chemistry ; 26(65): 14844-14851, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-32761643

RESUMO

This contribution describes the excited-state properties of an Osmium-complex when taken up into human cells. The complex 1 [Os(bpy)2 (IP-4T)](PF6 )2 with bpy=2,2'-bipyridine and IP-4T=2-{5'-[3',4'-diethyl-(2,2'-bithien-5-yl)]-3,4-diethyl-2,2'-bithiophene}imidazo[4,5-f][1,10]phenanthroline) can be discussed as a candidate for photodynamic therapy in the biological red/NIR window. The complex is taken up by MCF7 cells and localizes rather homogeneously within in the cytoplasm. To detail the sub-ns photophysics of 1, comparative transient absorption measurements were carried out in different solvents to derive a model of the photoinduced processes. Key to rationalize the excited-state relaxation is a long-lived 3 ILCT state associated with the oligothiophene chain. This model was then tested with the complex internalized into MCF7 cells, since the intracellular environment has long been suspected to take big influence on the excited state properties. In our study of 1 in cells, we were able to show that, though the overall model remained the same, the excited-state dynamics are affected strongly by the intracellular environment. Our study represents the first in depth correlation towards ex-vivo and in vivo ultrafast spectroscopy for a possible photodrug.

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