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Protein oxidation seems to be linked to constitutive autophagy: A sex study

机译:性别研究似乎证明蛋白质氧化与本构自噬有关

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Aim Although constitutive autophagy is linked to redox state and participates in cell homeostasis, it is scarcely known if redox state, autophagy, and lysosomal function depend on sex, a factor that largely influences health and diseases. Therefore, we evaluated the existence of sex differences in redox state and constitutive autophagy in rat tissues. Main methods 7 week old Sprague-Dawley rats were used to obtain organs. Malondialdehyde (MDA), and carbonylated proteins were measured by spectrophotometric methods for redox state assessment. The autophagy biomarkers Beclin-1, and microtubule-associated protein 1 light chain 3 (LC3), the mammalian target of rapamycin (mTOR; checkpoint in autophagic process), and the lysosomal associated membrane protein (LAMP-1; biomarker of lysosomes) were evaluated by Western blotting. Immunofluorescence analysis was also performed for LC3 and LAMP-1 colocalization. Key findings In the heart, Beclin-1, and LC3-II/LC3-I were higher in males than in females suggesting that the male heart has a major constitutive autophagy and this was linked with higher levels of carbonyl groups, indicating that protein oxidation could play a role. In the liver, it was found that LAMP-1 was higher in males and greatly colocalized with LC3 indicating a larger number of autophagolysosomes. None of the above parameters was significantly different in the kidneys of both sexes with the exception of MDA, which was significantly higher in females. Significance The above results suggest that sex differences exist in redox state and autophagy and they occur in an organ-specific way. Importantly, it seems that the protein oxidation is more linked with constitutive autophagy, at least in cardiac ventricles, in comparison with lipid peroxidation.
机译:目的尽管组成型自噬与氧化还原状态有关,并参与细胞稳态,但几乎不知道氧化还原状态,自噬和溶酶体功能是否取决于性别,而性别是影响健康和疾病的重要因素。因此,我们评估了大鼠组织中氧化还原状态和组成型自噬存在性别差异。主要方法使用7周大的Sprague-Dawley大鼠获取器官。通过分光光度法测量丙二醛(MDA)和羰基化蛋白的氧化还原状态。自噬生物标志物Beclin-1和微管相关蛋白1轻链3(LC3),雷帕霉素的哺乳动物靶标(mTOR;自噬过程中的检查点)和溶酶体相关膜蛋白(LAMP-1;溶酶体的生物标志物)通过蛋白质印迹评估。还对LC3和LAMP-1共定位进行了免疫荧光分析。主要发现心脏中,男性的Beclin-1和LC3-II / LC3-I高于女性,这表明男性心脏具有主要的组成型自噬,这与较高的羰基基团有关,表明蛋白质氧化可以发挥作用。在肝脏中,发现LAMP-1在男性中较高,并且与LC3高度共定位,表明自噬体的数量更多。除了MDA,上述参数在男女双方的肾脏中均无显着差异,而MDA在女性中明显更高。意义以上结果表明,性别差异存在于氧化还原状态和自噬中,并且以器官特异性方式发生。重要的是,与脂质过氧化相比,至少在心室中,蛋白质氧化似乎与组成型自噬联系更多。

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