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Age-related sex differences in the expression of important disease-linked mitochondrial proteins in mice.
Biology of Sex Differences ( IF 4.9 ) Pub Date : 2019-12-05 , DOI: 10.1186/s13293-019-0267-1
Michael Moschinger 1 , Karolina E Hilse 1 , Anne Rupprecht 1, 2 , Ute Zeitz 1 , Reinhold G Erben 1 , Thomas Rülicke 3 , Elena E Pohl 1
Affiliation  

The prevalence and progression of many illnesses, such as neurodegenerative and cardiovascular diseases, obesity, and cancer, vary between women and men, often in an age-dependent manner. A joint hallmark of these diseases is some type of mitochondrial dysfunction. While several mitochondrial proteins are known to be regulated by sex hormones, the levels of those proteins have not been systematically analyzed with regard to sex and age, and studies that consider sex and/or age differences in the protein expression are very rare. In this study, we compared the expression patterns of physiologically important mitochondrial proteins in female and male C57BL/6N mice of age cohorts frequently used in experiments. We found that sex-related differences in the expression of uncoupling proteins 1 and 3 (UCP1 and UCP3) occur in an age-dependent manner. The sex-specific expression of UCP1 and UCP3 in brown adipose tissue (BAT) was inversely correlated with differences in body weight. Expression of UCP4 in the brain, Complex I in the spleen, and Complex II in the brain and BAT was least affected by the sex of the mouse. We further demonstrated that there are serious limitations in using VDAC1 and actin as markers in western blot analyses, due to their sex- and age-specific fluctuations. Our results confirm that sex and age are important parameters and should be taken into account by researchers who examine the mechanistic aspects of diseases. HIGHLIGHTS: I.The levels of UCP1 and UCP3 protein expression differ between females and males in an age-dependent manner.II.Pre-pubertal expression of almost all proteins tested in this study does not depend on the sex of the mouse.III.Expression of VDAC1 and actin, which are often used as loading control proteins in western blot analysis, is tissue-specifically influenced by sex and age.

中文翻译:

与疾病相关的线粒体蛋白在小鼠中表达的年龄相关性别差异。

男女之间的许多疾病(例如神经退行性疾病和心血管疾病,肥胖症和癌症)的患病率和进展通常以年龄相关的方式变化。这些疾病的共同标志是某种类型的线粒体功能障碍。尽管已知几种线粒体蛋白受性激素调节,但尚未就性别和年龄对这些蛋白的水平进行系统的分析,而且在蛋白表达中考虑性别和/或年龄差异的研究非常少见。在这项研究中,我们比较了在实验中经常使用的年龄组的雌性和雄性C57BL / 6N小鼠中,生理上重要的线粒体蛋白的表达模式。我们发现,解偶联蛋白1和3(UCP1和UCP3)的表达中与性别相关的差异以年龄相关的方式出现。UCP1和UCP3在棕色脂肪组织(BAT)中的性别特异性表达与体重差异呈负相关。UCP4在大脑中的表达,脾脏中的复合物I以及大脑和BAT中的复合物II的表达受小鼠性别的影响最小。我们进一步证明,由于VDAC1和肌动蛋白的性别和年龄特异性波动,在蛋白质印迹分析中使用VDAC1和肌动蛋白作为标记存在严重局限性。我们的研究结果证实性别和年龄是重要的参数,研究疾病机理的研究人员应考虑性别和年龄。亮点:I.雌性和雄性中UCP1和UCP3蛋白的表达水平存在年龄依赖性。II。这项研究中测试的几乎所有蛋白的青春期前表达都与小鼠的性别无关。
更新日期:2020-04-22
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