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1.
Chem Biodivers ; 12(11): 1696-705, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26567947

RESUMO

We employed the primary cell model system as a first step toward establishing a method to assess the influence of ionizing radiation by using a combination of common and abundant metabolites. We applied X-ray irradiation amounts of 0, 1, and 5 Gy to the cells that were harvested 24, 48, or 72 h later, and profiled metabolites by 2D-NMR spectroscopy to sort out candidate molecules that could be used to distinguish the samples under different irradiation conditions. We traced metabolites stemming from the input ¹³C-glucose, identified twelve of them from the cell extracts, and applied statistical analysis to find out that all the metabolites, including glycine, alanine, and gluatamic acid, increased upon irradiation. The combinatorial use of the selected metabolites showed promising results where the product of signal intensities of alanine and lactate could differentiate samples according to the dose of X-ray irradiation. We hope that this work can form a base for treating radiation-poisoned patients in the future.


Assuntos
Espectroscopia de Ressonância Magnética , Cultura Primária de Células , Alanina/metabolismo , Relação Dose-Resposta à Radiação , Ácido Glutâmico/metabolismo , Glicina/metabolismo , Humanos , Raios X
2.
Free Radic Biol Med ; 61: 206-17, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23583701

RESUMO

The molecular inflammation hypothesis of aging proposes that redox dysregulation causes an age-related activation of NF-κB and its signaling to upregulate various proinflammatory genes. In the present study, we focused on the inactive form of the protein phosphastase 2A (PP2A). More specifically, we aimed to define the correlation between PP2A inactivation and NF-κB activation by age-related oxidative stress. Experimentations were designed to determine the effect of oxidative stress-induced PP2A inactivation on NF-κB activity, utilizing prooxidants t-BHP and AAPH, the PTP inhibitor Na3VO4, and the PP2A inhibitor Calyculin A and PP2A siRNA, in HEK293T cells. We also assessed the phosphorylation of PP2A catalytic subunit (PP2Ac) and the activities of PP2A and NF-κB in aged rat kidney, utilizing aging-retarding 40% calorie restriction (CR) -60% of food intake and inflammation-triggering LPS paradigms. Results revealed that an oxidative stress-induced PTK/PTP imbalance led to phosphorylation of PP2Ac, following exposures to t-BHP, AAPH, and Na3VO4 in HEK293T cells. Subsequently, we found that Calyculin A and PP2A siRNA activates NIK/IKK and MAPKs, leading to upregulation of NF-κB and its dependent oxidative stress. Also, the contrasting relation between PP2A inactivation and NF-κB activation was confirmed by AAPH-induced oxidative status in mice, and non-induced normal status or LPS-induced inflammatory status in aged rats while the antioxidative, anti-inflammatory, anti-aging effects of CR significantly blunted these actions. Thus, we present evidence that PP2A inactivation via PTK/PTP imbalance provoked by oxidative stress causes NF-κB activation, which contributes to the accumulation of oxidative stress in aged rat kidney.


Assuntos
Envelhecimento/metabolismo , Rim/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Proteína Fosfatase 2/fisiologia , Animais , Células HEK293 , Humanos , Masculino , Toxinas Marinhas , Camundongos , Camundongos Endogâmicos C57BL , Oxazóis/farmacologia , Proteínas Tirosina Quinases/fisiologia , Ratos , Ratos Endogâmicos F344
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