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Cell Death Dis ; 3: e401, 2012 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-23059820

RESUMO

The naturally occurring polyamine spermidine (Spd) has recently been shown to promote longevity across species in an autophagy-dependent manner. Here, we demonstrate that Spd improves both survival and locomotor activity of the fruit fly Drosophila melanogaster upon exposure to the superoxide generator and neurotoxic agent paraquat. Although survival to a high paraquat concentration (20 mM) was specifically increased in female flies only, locomotor activity and survival could be rescued in both male and female animals when exposed to lower paraquat levels (5 mM). These effects are dependent on the autophagic machinery, as Spd failed to confer resistance to paraquat-induced toxicity and locomotor impairment in flies deleted for the essential autophagic regulator ATG7 (autophagy-related gene 7). Spd treatment did also protect against mild doses of another oxidative stressor, hydrogen peroxide, but in this case in an autophagy-independent manner. Altogether, this study establishes that the protective effects of Spd can be exerted through different pathways that depending on the oxidative stress scenario do or do not involve autophagy.


Assuntos
Autofagia/efeitos dos fármacos , Drosophila melanogaster/efeitos dos fármacos , Espermidina/farmacologia , Animais , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Resistência a Medicamentos , Feminino , Herbicidas/toxicidade , Peróxido de Hidrogênio/toxicidade , Masculino , Atividade Motora/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Paraquat/toxicidade , Enzimas Ativadoras de Ubiquitina/metabolismo
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