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蛋白质组学分析揭示了先天性低有氧能力大鼠心脏中能量代谢紊乱和氧化应激升高。

Proteomic analysis reveals perturbed energy metabolism and elevated oxidative stress in hearts of rats with inborn low aerobic capacity.

机构信息

Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, UK.

出版信息

Proteomics. 2011 Aug;11(16):3369-79. doi: 10.1002/pmic.201000593.

DOI:10.1002/pmic.201000593
PMID:21751351
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3319703/
Abstract

Selection on running capacity has created rat phenotypes of high-capacity runners (HCRs) that have enhanced cardiac function and low-capacity runners (LCRs) that exhibit risk factors of metabolic syndrome. We analysed hearts of HCRs and LCRs from generation 22 of selection using DIGE and identified proteins from MS database searches. The running capacity of HCRs was six-fold greater than LCRs. DIGE resolved 957 spots and proteins were unambiguously identified in 369 spots. Protein expression profiling detected 67 statistically significant (p<0.05; false discovery rate <10%, calculated using q-values) differences between HCRs and LCRs. Hearts of HCR rats exhibited robust increases in the abundance of each enzyme of the β-oxidation pathway. In contrast, LCR hearts were characterised by the modulation of enzymes associated with ketone body or amino acid metabolism. LCRs also exhibited enhanced expression of antioxidant enzymes such as catalase and greater phosphorylation of α B-crystallin at serine 59, which is a common point of convergence in cardiac stress signalling. Thus, proteomic analysis revealed selection on low running capacity is associated with perturbations in cardiac energy metabolism and provided the first evidence that the LCR cardiac proteome is exposed to greater oxidative stress.

摘要

选择对跑步能力的影响产生了高能力跑步者(HCR)和低能力跑步者(LCR)的大鼠表型,前者具有增强的心脏功能,后者表现出代谢综合征的危险因素。我们使用 DIGE 分析了第 22 代选择的 HCR 和 LCR 心脏,并从 MS 数据库搜索中鉴定了蛋白质。HCR 的跑步能力是 LCR 的六倍。DIGE 解析了 957 个斑点,在 369 个斑点中明确鉴定了蛋白质。蛋白质表达谱检测到 HCR 和 LCR 之间有 67 个统计学上显著的差异(p<0.05;使用 q 值计算的假发现率<10%)。HCR 大鼠的心脏中β氧化途径的每个酶的丰度都显著增加。相比之下,LCR 心脏的特征是与酮体或氨基酸代谢相关的酶的调节。LCR 还表现出抗氧化酶如过氧化氢酶的表达增强,以及α B-晶体蛋白丝氨酸 59 处磷酸化的增加,这是心脏应激信号转导的一个共同汇聚点。因此,蛋白质组学分析表明,对低跑步能力的选择与心脏能量代谢的紊乱有关,并首次提供了证据表明 LCR 心脏蛋白质组受到更大的氧化应激。

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