Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Cardiovascular Research, Institute of Pharmacology, Berlin, Germany.
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Cardiovascular Research, Institute of Pharmacology, Berlin, Germany; Proteome Factory AG, Berlin, Germany.
J Proteomics. 2018 Apr 30;178:43-56. doi: 10.1016/j.jprot.2017.12.005. Epub 2017 Dec 19.
We investigated sex differences in cardiac protein patterns of intact and castrated mice using proteomics and 1D and 2D immunoblotting. To exclude differences concerning developmental aspects gonadectomy was conducted in mature mice at the age of three months. The main sex-related regulation in the protein pattern of the myocardium occurred for proteins involved in metabolic processes whereas only few proteins involved in other pathways underwent a regulation. Many regulated proteins (2/3) displayed a characteristic V form, which means that these proteins are up- or down-regulated in sexually mature compared to young mice and are back-regulated after castration, emphasizing a direct regulation by gonadal hormones. Several other spots (1/3) showed the same male/female regulation or a drastic increase in male/female spot intensity ratio after castration, suggesting either a regulation independent of sex hormones or a removal of an inhibiting feedback mechanism by gonadectomy. Technically, we found that it cannot be expected that a single spot contains only one protein species and that one protein is present in only one spot. We thus propose for proteomic investigations to identify/quantify all spots of a 2-DE pattern to obtain information about protein speciation and its potential importance for function and pathology.
Sex related differences in cardiovascular disease, including risk factors, disease manifestation and outcomes, are far from being well understood, and improved biological understanding of these differences in the healthy myocardium is of great importance. We investigated sex related changes of myocardial protein pattern in intact and castrated mice at different ages and found metabolic proteins to be highly regulated, some of which independently from gonadal hormones.
我们使用蛋白质组学和一维及二维免疫印迹技术研究了完整和去势雄性和雌性小鼠心脏蛋白图谱的性别差异。为了排除与发育相关的差异，在 3 月龄的成熟小鼠中进行了去势手术。心肌蛋白图谱中主要的性别相关调控发生在代谢过程相关的蛋白，而其他途径的蛋白只有少数发生调控。许多受调控的蛋白（2/3）呈现出特征性的 V 形，这意味着这些蛋白在性成熟的小鼠中上调或下调，而去势后又被下调，这强调了性腺激素的直接调控作用。还有一些蛋白（1/3）显示出相同的雌雄调控或去势后雌雄蛋白点强度比急剧增加，提示要么是独立于性激素的调控，要么是去势切除了抑制性反馈机制。从技术上讲，我们发现不能期望一个蛋白点只含有一种蛋白，而且一种蛋白只存在于一个点中。因此，我们建议在蛋白质组学研究中鉴定/定量 2-DE 图谱中的所有点，以获得蛋白物种的信息及其对功能和病理的潜在重要性。
心血管疾病的性别差异，包括风险因素、疾病表现和结果，远未被充分理解，而对健康心肌中这些差异的生物学理解的提高具有重要意义。我们研究了不同年龄的完整和去势雄性和雌性小鼠心肌蛋白图谱的性别相关变化，发现代谢蛋白高度调控，其中一些蛋白独立于性腺激素。
