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1.
Mol Cell Biochem ; 339(1-2): 63-77, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20058056

RESUMO

It has been shown that changes in spectrin distribution in early apoptosis preceded changes in membrane asymmetry and phosphatidylserine (PS) exposure. PKCtheta was associated with spectrin during these changes, suggesting a possible role of spectrin/PKCtheta aggregation in regulation of early apoptotic events. Here we dissect this hypothesis using Jurkat T and HL60 cell lines as model systems. Immunofluorescent analysis of alphaIIbetaII spectrin arrangement in Jurkat T and HL60 cell lines revealed the redistribution of spectrin and PKCtheta into a polar aggregate in early apoptosis induced by fludarabine/mitoxantrone/dexamethasone (FND). The appearance of an alphaIIbetaII spectrin fraction that was insoluble in a non-ionic detergent (1% Triton X-100) was observed concomitantly with spectrin aggregation. The changes were observed within 2 h after cell exposure to FND, and preceded PS exposure. The changes seem to be restricted to spectrin and not to other cytoskeletal proteins such as actin or vimentin. In studies of the mechanism of these changes, we found that (i) neither changes in apoptosis regulatory genes (e.g., Bcl-2 family proteins) nor changes in cytoskeleton-associated proteins were detected in gene expression profiling of HL60 cells after the first hour of FND treatment, (ii) caspase-3, -7, -8, and -10 had minor involvement in the early apoptotic rearrangement of spectrin/PKCtheta, and (iii) spectrin aggregation was shown to be partially dependent on PKCtheta activity. Our results indicate that spectrin/PKCtheta aggregate formation is related to an early stage in drug-induced apoptosis and possibly may be regulated by PKCtheta activity. These findings indicate that spectrin/PKCtheta aggregation could be considered as a hallmark of early apoptosis and presents the potential to become a useful diagnostic tool for monitoring efficiency of chemotherapy as early as 24 h after treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Isoenzimas/metabolismo , Proteína Quinase C/metabolismo , Espectrina/metabolismo , Actinas/metabolismo , Western Blotting , Caspase 3/metabolismo , Inibidores de Caspase , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Dexametasona/administração & dosagem , Citometria de Fluxo , Imunofluorescência , Células HL-60 , Humanos , Células Jurkat , Mitoxantrona/administração & dosagem , Octoxinol , Proteína Quinase C-theta , Multimerização Proteica , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Vimentina/metabolismo
2.
Rocz Panstw Zakl Hig ; 58(1): 287-93, 2007.
Artigo em Polonês | MEDLINE | ID: mdl-17711124

RESUMO

Fish meat content high nutritive value and essential polyunsaturated fatty acids, while low consumption of fish and fishery products in Poland. Fat meat of Baltic sea fish can also contain higher levels of dioxins and organochlorinated contaminants. Consumption of fish and fishery products in Poland ought to include different species from various catch areas.


Assuntos
Poluentes Ambientais/análise , Produtos Pesqueiros/análise , Contaminação de Alimentos/análise , Tecido Adiposo/química , Animais , Dieta , Dioxinas/análise , Dioxinas/intoxicação , Ácidos Graxos Ômega-3 , Peixes , Manipulação de Alimentos , Humanos , Intoxicação por Mercúrio/prevenção & controle , Polônia , Medição de Risco , Fatores de Risco
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