SummaryCaloric restriction is the most effective non-genetic intervention to enhance lifespan known to date. A major research interest has been the development of therapeutic strategies capable of promoting the beneficial results of this dietary regimen. In this sense, we propose that compounds that decrease the efficiency of energy conversion, such as mitochondrial uncouplers, can be caloric restriction mimetics. Treatment of mice with low doses of the protonophore 2,4-dinitrophenol promotes enhanced tissue respiratory rates, improved serological glucose, triglyceride and insulin levels, decrease of reactive oxygen species levels and tissue DNA and protein oxidation, as well as reduced body weight. Importantly, 2,4-dinitrophenol-treated animals also presented enhanced longevity. Our results demonstrate that mild mitochondrial uncoupling is a highly effective in vivo antioxidant strategy, and describe the first therapeutic intervention capable of effectively reproducing the physiological, metabolic and lifespan effects of caloric restriction in healthy mammals.
The genus Trichoderma is a potential biocontrol agent against several phytopathogenic fungi. One parameter for its successful use is an efficient coiling process followed by a substantial production of hydrolytic enzymes. The interaction between fifteen isolates of Trichoderma harzianum and the soil-borne plant pathogen, Rhizoctonia solani, was studied by light microscopy and transmission electron microscopy (TEM). Macroscopic observations of fungal growth in dual cultures revealed that growth inhibition of the pathogen occurred soon after contact with the antagonist. All T. harzianum isolates tested exhibited coiling around the hyphae of R. solani. The strains ALL23, ALL40, ALL41, ALL43 and ALL49 did not differ in coiling frequency and gave equal coiling performances. No correlation between coiling frequency and the production of cell wall-degrading chitinases, N-acetyl-beta-D-glucosaminidase and beta-1,3-glucanases, was found.
Recebido em 10/10/05; aceito em 20/4/06; publicado na web em 10/1/07 DIETETIC ANTIOXIDANTS: CONTROVERSIES AND PERSPECTIVES The generation of reactive oxygen and nitrogen species (ROS and RNS) during metabolism is capable of damaging cellular biomolecules. To be protected against oxidative injury, cells evolved complex cellular defense mechanisms and the capability to use exogenous antioxidants to eliminate ROS/RNS. The potential role of micronutrients as antioxidants (vitamin C, vitamin E, carotenoids and poliphenols) has stimulated intense research efforts. In various human supplementation studies, however, these compounds presented pro-oxidant effects at high doses for most risk groups. Therefore, more studies about the bioavailability, tissue uptake, metabolism and biological activities should be performed before establishing recommendations for disease prevention.Keywords: antioxidant vitamins; carotenoids; poliphenols. INTRODUÇÃOOs organismos vivos interagem com o meio ambiente visando manter um ambiente interno que favoreça a sobrevivência, o crescimento e a reprodução. O oxigênio molecular (O 2 ) obtido da atmosfera é vital para organismos aeróbios; contudo, espécies reativas formadas intracelularmente a partir do oxigênio ameaçam a integridade celular por meio da oxidação de biomoléculas, e podem comprometer processos biológicos importantes 1 .O dano oxidativo de biomoléculas pode levar à inativação enzimática, mutação, ruptura de membrana, ao aumento na aterogenicidade de lipoproteínas plasmáticas de baixa densidade e à morte celular. Estes efeitos tóxicos do oxigênio têm sido associados ao envelhecimento e ao desenvolvimento de doenças crôni-cas, inflamatórias e degenerativas 2 .A despeito deste paradoxo, a vida aeróbia tornou-se possível graças às adaptações biológicas que levaram ao desenvolvimento de defesas antioxidantes contra a toxicidade do oxigênio e espécies derivadas deste. As adaptações biológicas às mudanças do meio ambiente guiam o processo evolutivo. Neste sentido, as adaptações podem ser definidas como características que se tornam aumentadas e mantidas sob seleção 1 .Embora as defesas antioxidantes endógenas sejam efetivas, não são infalíveis, e constantemente há formação de espécies reativas de oxigênio e de nitrogênio (ROS/RNS) que interagem em diferentes níveis com o ambiente celular antes de serem eliminadas, o que, à primeira vista, pode parecer uma falha evolutiva. Todavia, há evidências recentes de que um certo nível destas espécies é imprescindível para muitas funções fisiológicas. Por ex., o enovelamento de proteínas nascentes no retículo endoplasmático ocorre em um meio mais oxidante que o restante da célula para a formação de pontes dissulfeto 1 . Também, muitos genes são transcritos após oxidação transitória e baixas concentrações de alguns oxidantes estimulam a proliferação celular, como exemplificado pela adição de 1 μM de H 2 O 2 à cultura de células 3 .Os componentes celulares não são protegidos totalmente por antioxidantes endógenos, e é bem estabelecido que antioxidant...
Enhanced mitochondrial biogenesis promoted by eNOS activation is believed to play a central role in the beneficial effects of calorie restriction (CR). Since treatment of mice with dinitrophenol (DNP) promotes health and lifespan benefits similar to those observed in CR, we hypothesized that it could also impact biogenesis. We found that DNP and CR increase citrate synthase activity, PGC-1α, cytochrome c oxidase and mitofusin-2 expression, as well as fasting plasma levels of NO• products. In addition, eNOS and Akt phosphorylation in skeletal muscle and visceral adipose tissue was activated in fasting CR and DNP animals. Overall, our results indicate that systemic mild uncoupling activates eNOS and Akt-dependent pathways leading to mitochondrial biogenesis.
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