RESUMO
A progressively expanded literature has been devoted in the past years to the noxious or beneficial effects of electromagnetic field (EMF) to Alzheimer׳s disease (AD). This study concerns the relationship between electromagnetic pulse (EMP) exposure and the occurrence of AD in rats and the underlying mechanisms, focusing on the role of oxidative stress (OS). 55 healthy male Sprague Dawley (SD) rats were used and received continuous exposure for 8 months. Morris water maze (MWM) test was conducted to test the ability of cognitive and memory. The level of OS was detected by superoxide dismutase (SOD) activity and glutathione (GSH) content. We found that long-term EMP exposure induced cognitive damage in rats. The content of ß-amyloid (Aß) protein in hippocampus was increased after long-term EMP exposure. OS of hippocampal neuron was detected. Western blotting and immunohistochemistry (IHC) assay showed that the content of Aß protein and its oligomers in EMP-exposed rats were higher than that of sham-exposed rats. The content of Beta Site App Cleaving Enzyme (BACE1) and microtubule-associated protein 1 light chain 3-II (LC3-II) in EMP-exposed rats hippocampus were also higher than that of sham-exposed rats. SOD activity and GSH content in EMP-exposed rats were lower than sham-exposed rats (p<0.05). Several mechanisms were proposed based on EMP exposure-induced OS, including increased amyloid precursor protein (APP) aberrant cleavage. Although further study is needed, the present results suggest that long-term EMP exposure is harmful to cognitive ability in rats and could induce AD-like pathological manifestation.
Assuntos
Doença de Alzheimer/metabolismo , Doença de Alzheimer/psicologia , Secretases da Proteína Precursora do Amiloide/efeitos da radiação , Peptídeos beta-Amiloides/efeitos da radiação , Precursor de Proteína beta-Amiloide/efeitos da radiação , Ácido Aspártico Endopeptidases/efeitos da radiação , Cognição/efeitos da radiação , Campos Eletromagnéticos , Estresse Oxidativo/efeitos da radiação , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Ácido Aspártico Endopeptidases/metabolismo , Cognição/fisiologia , Modelos Animais de Doenças , Hipocampo/metabolismo , Hipocampo/efeitos da radiação , Masculino , Aprendizagem em Labirinto/efeitos da radiação , Ratos , Ratos Sprague-DawleyRESUMO
Beta-amyloid precursor protein (APP) is the precursor of beta-amyloid (Abeta), which is implicated in Alzheimer's disease pathogenesis. APP complements amyloid precursor-like protein 2 (APLP2), and together they play essential physiological roles. Phosphorylation at the Thr(668) residue of APP (with respect to the numbering conversion for the APP 695 isoform) and the Thr(736) residue of APLP2 (with respect to the numbering conversion for the APLP2 763 isoform) in their cytoplasmic domains acts as a molecular switch for their protein-protein interaction and is implicated in neural function(s) and/or Alzheimer's disease pathogenesis. Here we demonstrate that both APP and APLP2 can be phosphorylated by JNK at the Thr(668) and Thr(736) residues, respectively, in response to cellular stress. X11-like (X11L, also referred to as X11beta and Mint2), which is a member of the mammalian LIN-10 protein family and a possible regulator of Abeta production, elevated APP and APLP2 phosphorylation probably by facilitating JNK-mediated phosphorylation, whereas other members of the family, X11 and X11L2, did not. These observations revealed an involvement of X11L in the phosphorylation of APP family proteins in cellular stress and suggest that X11L protein may be important in the physiology of APP family proteins as well as in the regulation of Abeta production.
Assuntos
Precursor de Proteína beta-Amiloide/metabolismo , Caderinas/metabolismo , Proteínas de Transporte/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno , Proteínas do Tecido Nervoso/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Precursor de Proteína beta-Amiloide/efeitos da radiação , Anisomicina/farmacologia , Sítios de Ligação , Caderinas/efeitos da radiação , Proteínas de Transporte/efeitos da radiação , Linhagem Celular , Humanos , Rim , MAP Quinase Quinase 4 , Quinases de Proteína Quinase Ativadas por Mitógeno/efeitos dos fármacos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/efeitos da radiação , Proteínas do Tecido Nervoso/efeitos da radiação , Fosforilação , Isoformas de Proteínas/metabolismo , Proteínas Recombinantes/metabolismo , Sorbitol/farmacologia , Treonina , Transfecção , Raios UltravioletaRESUMO
Formalin fixation reduces beta-amyloid precursor protein (beta APP) immunoreactivity which restricts its study in archival tissue. Formic acid pretreatment has previously been used in an attempt to overcome this problem, but makes the sections very friable. In the present study, a microwave antigen retrieval method has been compared with formic acid pretreatment for retrieving beta APP immunoreactivity in formalin-fixed, paraffin-embedded human brain tissue. Microwave treatment resulted in superior retrieval of beta APP antigenicity in dystrophic neurites in Alzheimer's disease and in injured axons after head injury, using antibodies to three different epitopes. Unlike formic acid, microwave treatment causes minimal adverse effects on the strength and slide adhesion of the sections.