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1.
J Biol Chem ; 290(29): 18090-18101, 2015 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-26032421

RESUMO

Degradation of ornithine decarboxylase, the rate-limiting enzyme of polyamine biosynthesis, is promoted by the protein antizyme. Expression of antizyme is positively regulated by rising polyamine concentrations that induce a +1 translational frameshift required for production of the full-length protein. Antizyme itself is negatively regulated by the antizyme inhibitor. In our study, the regulation of Caenorhabditis elegans antizyme was investigated, and the antizyme inhibitor was identified. By applying a novel GFP-based method to monitor antizyme frameshifting in vivo, we show that the induction of translational frameshifting also occurs under stressful conditions. Interestingly, during starvation, the initiation of frameshifting was independent of polyamine concentrations. Because frameshifting was also prevalent in a polyamine auxotroph double mutant, a polyamine-independent regulation of antizyme frameshifting is suggested. Polyamine-independent induction of antizyme expression was found to be negatively regulated by the peptide transporter PEPT-1, as well as the target of rapamycin, but not by the daf-2 insulin signaling pathway. Stress-dependent expression of C. elegans antizyme occurred morely slowly than expression in response to increased polyamine levels, pointing to a more general reaction to unfavorable conditions and a diversion away from proliferation and reproduction toward conservation of energy. Interestingly, antizyme expression was found to drastically increase in aging individuals in a postreproductive manner. Although knockdown of antizyme did not affect the lifespan of C. elegans, knockdown of the antizyme inhibitor led to a significant reduction in lifespan. This is most likely caused by an increase in antizyme-mediated degradation of ornithine decarboxylase-1 and a resulting reduction in cellular polyamine levels.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Mudança da Fase de Leitura do Gene Ribossômico , Poliaminas/metabolismo , Proteínas/genética , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Longevidade , Ornitina Descarboxilase/metabolismo , Proteínas/metabolismo , Proteólise , Reprodução , Estresse Fisiológico
2.
Biomed Res Int ; 2015: 351289, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25722976

RESUMO

Apicomplexan parasites cause infectious diseases that are either a severe public health problem or an economic burden. In this paper we will shed light on how oxidative stress can influence the host-pathogen relationship by focusing on three major diseases: babesiosis, coccidiosis, and toxoplasmosis.


Assuntos
Babesia/metabolismo , Cryptosporidium/metabolismo , Estresse Oxidativo , Toxoplasma/metabolismo , Animais , Babesia/patogenicidade , Babesiose/metabolismo , Babesiose/parasitologia , Babesiose/patologia , Coccidiose/metabolismo , Coccidiose/parasitologia , Coccidiose/patologia , Cryptosporidium/patogenicidade , Interações Hospedeiro-Parasita , Humanos , Toxoplasma/patogenicidade , Toxoplasmose/metabolismo , Toxoplasmose/parasitologia , Toxoplasmose/patologia
3.
PLoS One ; 8(4): e60731, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23593298

RESUMO

Glutathione (GSH) and GSH-dependent enzymes play a key role in cellular detoxification processes that enable organism to cope with various internal and environmental stressors. However, it is often not clear, which components of the complex GSH-metabolism are required for tolerance towards a certain stressor. To address this question, a small scale RNAi-screen was carried out in Caenorhabditis elegans where GSH-related genes were systematically knocked down and worms were subsequently analysed for their survival rate under sub-lethal concentrations of arsenite and the redox cycler juglone. While the knockdown of γ-glutamylcysteine synthetase led to a diminished survival rate under arsenite stress conditions, GSR-1 (glutathione reductase) was shown to be essential for survival under juglone stress conditions. gsr-1 is the sole GSR encoding gene found in C. elegans. Knockdown of GSR-1 hardly affected total glutathione levels nor reduced glutathione/glutathione disulphide (GSH/GSSG) ratio under normal laboratory conditions. Nevertheless, when GSSG recycling was impaired by gsr-1(RNAi), GSH synthesis was induced, but not vice versa. Moreover, the impact of GSSG recycling was potentiated under oxidative stress conditions, explaining the enormous effect gsr-1(RNAi) knockdown had on juglone tolerance. Accordingly, overexpression of GSR-1 was capable of increasing stress tolerance. Furthermore, expression levels of SKN-1-regulated GSR-1 also affected life span of C. elegans, emphasising the crucial role the GSH redox state plays in both processes.


Assuntos
Caenorhabditis elegans/enzimologia , Caenorhabditis elegans/fisiologia , Glutationa Redutase/metabolismo , Longevidade , Estresse Oxidativo , Animais , Arsenitos/toxicidade , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Glutationa/metabolismo , Glutationa Redutase/deficiência , Glutationa Redutase/genética , Longevidade/efeitos dos fármacos , Naftoquinonas/toxicidade , Oxidantes/toxicidade , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenótipo , Interferência de RNA , Estresse Fisiológico/efeitos dos fármacos
4.
J Biol Chem ; 288(15): 10661-71, 2013 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-23449979

RESUMO

Ufm1 (ubiquitin-fold modifier 1) is the most recently identified member of the ubiquitin-like protein family. We characterized the Ufm1 cascade of the model organism Caenorhabditis elegans in terms of function and analyzed interactions of the involved proteins in vitro and in vivo. Furthermore, we investigated the phenotypes of the deletion mutants uba5(ok3364) (activating enzyme of Ufm1) and ufc1(tm4888) (conjugating enzyme of Ufm1). The viable deletion mutants showed a decrease in reproduction, development, life span, and a reduced survival under heavy metal stress. However, an increased survival rate under pathogenic, oxidative, heat, and endoplasmic reticulum stress was observed. We propose that the Ufm1 cascade negatively regulates the IRE1-mediated unfolded protein response.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Deleção de Genes , Resposta ao Choque Térmico/fisiologia , Longevidade/fisiologia , Estresse Oxidativo/fisiologia , Reprodução/fisiologia , Resposta a Proteínas não Dobradas/fisiologia
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