• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Localization and quantitation of oxidative damage in skeletal muscle from aging rhesus monkeys: Attenuation by caloric restriction.
【24h】

Localization and quantitation of oxidative damage in skeletal muscle from aging rhesus monkeys: Attenuation by caloric restriction.

机译：衰老恒河猴骨骼肌氧化损伤的定位和定量：受热量限制的衰减。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Sarcopenia refers to an involuntary loss of skeletal muscle mass, which consequently results in loss of muscle strength and an increase in physical frailty in older persons. Applied to sarcopenia, the oxidative stress/damage hypothesis of aging would predict that loss of mass and functional performance of skeletal muscle with age is correlated with increased levels of oxidative stress and subsequent damage. In laboratory rodents, caloric restriction (CR) extends maximum lifespan and retards the appearance of a broad spectrum of age-associated pathophysiological changes. In skeletal muscle, CR retards several age-dependent physiological and biochemical changes, including increased steady-state levels of oxidative damage to lipids, DNA, and proteins. To date no studies have characterized oxidative damage in aging mammalian skeletal muscle from a histological standpoint. The well-established ferric nitrilotriacetate (Fe-NTA) model of iron-induced free radical injury was utilized as a positive control for markers of age-related oxidative stress and damage by demonstrating that the intensity of immunolabeling at both the light and EM levels correlated with increased biochemically measured lipid peroxidation products and protein carbonyl content. Furthermore, the data suggested that the mechanism of acute nephrotoxicity of Fe-NTA involves mitochondrial and nuclear oxidative damage. We employed immunogold light and electron microscopic (EM) techniques utilizing antibodies raised against 4-hydroxy-2-nonenal (HNE)-modified proteins, dinitrophenol (DNP), and nitrotyrosine (NT) to quantitate and localize oxidative damage in aging rhesus monkey vastus lateralis skeletal muscle. In animals ranging in age from 2--34 years old, a 4-fold maximal increase in levels of HNE-modified proteins was observed. Likewise, carbonyl levels increased ∼2-fold with aging. Comparing 17--23 year old normally fed to age-matched monkeys subjected to CR for 10 years, levels of HNE-modified proteins, carbonyls, and nitrotyrosine in skeletal muscle from the CR group were significantly less than control group values. Oxidative damage specifically localized to myofibrils. Accumulation of lipid peroxidation-derived aldehydes, such as malondialdehyde (MDA) and 4-hydroxy-2-alkenals (4-HDA), and protein carbonyls were measured biochemically and confirmed the morphological data. This study is the first to quantitate morphologically and localize the age-dependent accrual of oxidative damage in mammalian skeletal muscle and to demonstrate that oxidative damage in primates is lowered by CR.
机译：肌肉减少症是指骨骼肌质量的非自愿丧失，其结果是导致老年人肌肉力量的丧失和身体虚弱的增加。应用于肌肉减少症，衰老的氧化应激/损伤假说将预测骨骼肌的质量和功能丧失随年龄的增长与氧化应激水平升高和随后的损伤相关。在实验室啮齿动物中，热量限制（CR）可延长最大寿命，并延缓与年龄相关的病理生理变化的广泛出现。在骨骼肌中，CR延缓了几种与年龄有关的生理和生化变化，包括增加了对脂质，DNA和蛋白质的氧化损伤的稳态水平。迄今为止，从组织学的角度来看，尚无研究描述衰老的哺乳动物骨骼肌的氧化损伤。通过证明轻度和EM水平的免疫标记强度均相关，将公认的铁诱导的自由基引起的次氮基三乙酸铁（Fe-NTA）模型用作年龄相关的氧化应激和损伤标记的阳性对照。生化测定的脂质过氧化产物和蛋白质羰基含量增加。此外，数据表明Fe-NTA的急性肾毒性机制涉及线粒体和核氧化损伤。我们采用免疫金光和电子显微镜（EM）技术，利用针对4-羟基-2-壬烯醛（HNE）修饰的蛋白质，二硝基苯酚（DNP）和硝化酪氨酸（NT）的抗体来定量和定位衰老猕猴巨大体内的氧化损伤外侧骨骼肌。在2-34岁之间的动物中，观察到HNE修饰蛋白的水平增加了4倍。同样，羰基水平随老化而增加约2倍。正常情况下，将17--23岁的正常人喂给年龄相匹配的接受CR 10年的猴子，CR组骨骼肌中HNE修饰的蛋白质，羰基和硝基酪氨酸的水平显着低于对照组。氧化损伤特别局限于肌原纤维。生化测定脂质过氧化衍生的醛，例如丙二醛（MDA）和4-羟基-2-烯醛（4-HDA）和蛋白羰基的积累，并确认了形态学数据。这项研究是第一个从形态学上定量并定位哺乳动物骨骼肌氧化损伤的年龄依赖性累积，并证明CR可以降低灵长类动物的氧化损伤。

著录项

  • 作者

    Zainal, Theodor Abidin.;

  • 作者单位

    The University of Wisconsin - Madison.;

  • 授予单位 The University of Wisconsin - Madison.;
  • 学科 Health Sciences Nutrition.;Health Sciences Human Development.
  • 学位 Ph.D.
  • 年度 1999
  • 页码 152 p.
  • 总页数 152
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号