• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Modulation of expression of pro- and anti-apoptotic genes during streptozotocin-induced oxidative stress in hyperglycemic mouse kidneys.
【24h】

Modulation of expression of pro- and anti-apoptotic genes during streptozotocin-induced oxidative stress in hyperglycemic mouse kidneys.

机译：链脲佐菌素诱导的高血糖小鼠肾脏氧化应激过程中促凋亡和抗凋亡基因表达的调节。

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

Decades of intense research has shown that hyperglycemia results in the generation of reactive oxygen species, ultimately leading to increased oxidative stress in a variety of tissues. In the absence of an efficient antioxidant counteracting system, target tissues go through a redox imbalance, leading to the activation of stress-responsive intracellular signaling pathways and major consequences of such perturbations translate into deregulated expression of cell-survival and cell-death regulating genes in vivo and in vitro. Persistent deregulation of such pathways can cause organ dysfunction, and are presumed to be responsible for the late complications of diabetes. Most studies hold hyperglycemia-induced oxidative stress as the 'cause', and premature onset of apoptosis as the 'effect'. This 'cause and effect' axis ultimately initiates the development and progression of macro and microvascular complications including diabetic nephropathy. This acute in vivo study was designed to investigate: (i) whether streptozotocin(STZ)-induced hyperglycemia can cause oxidative stress in kidneys and if so (ii) whether acute oxidative stress can influence pro- and anti-apoptotic genes and contribute to kidney-injury. Eight months old mice (female B6C3F1) were treated with STZ (dissolved in citrate buffer 100 mg/kg, ip) for six consecutive days and all the animals were sacrificed on day-7. Control animals received vehicle alone (Citrate buffer, pH 4.0). Blood and kidneys were collected for further analysis. All the STZ-exposed animals showed massive hyperglycemia (average blood glucose: Control- 120+/-10 STZ- 395.5+/-50 in mg/dl), elevated BUN concentrations (Control- 30+/-2 STZ- 121+/-11 in mg/dl), increased lipid peroxidation (Control- 8.3+/-1 STZ- 19.1+/-2 nmol/gm. protein), and DNA fragmentation (%Control- 100+/-11 STZ- 330+/-18). In contrast to these parameters, glutathione peroxidase (Enzyme level U/g. protein: Control 431+/-19 STZ- 291+/-15) and SOD activities (Control 414+/-9 STZ- 183+/-10) declined in kidney tissues. Along with the antioxidant team, expression of anti-death genes, Bcl-2 and Bcl-XL proteins decreased and mitochondria-sensitive pro-apoptotic molecular marker Cyt C level dramatically increased. In summary, this study shows that even a short-term hyperglycemia-induced oxidative stress may perturb the tissue biochemistry favorable for apoptosis and long-term impact of this may translate into serious nephrotoxic consequences.
机译：数十年的大量研究表明，高血糖会导致产生活性氧，最终导致各种组织的氧化应激增加。在缺乏有效的抗氧化剂抵消系统的情况下，靶组织会经历氧化还原失衡，从而导致应激反应性细胞内信号转导通路的激活，这种扰动的主要后果转化为细胞存活基因和细胞死亡调控基因的失调表达。体内和体外。此类通路的持续失调可导致器官功能障碍，并被认为是糖尿病晚期并发症的原因。大多数研究认为高血糖引起的氧化应激是“原因”，而凋亡的过早发作则是“效应”。这个“因果关系”轴最终启动了包括糖尿病肾病在内的大血管和微血管并发症的发生和发展。这项急性体内研究旨在调查：（i）链脲佐菌素（STZ）诱导的高血糖症是否会引起肾脏的氧化应激；如果是，则（ii）急性氧化应激是否会影响促凋亡和抗凋亡基因并有助于肾脏-受伤。将八个月大的小鼠（雌性B6C3F1）用STZ（溶于100 mg / kg柠檬酸盐缓冲液，腹腔注射）处理连续六天，所有动物在第7天处死。对照动物仅接受媒介物（柠檬酸盐缓冲液，pH 4.0）。收集血液和肾脏以进行进一步分析。所有暴露于STZ的动物均表现出大量高血糖症（平均血糖：对照120 +/- 10 STZ- 395.5 +/- 50 mg / dl），BUN浓度升高（对照30 +/- 2 STZ- 121 + / -11（mg / dl），脂质过氧化增加（对照-8.3 +/- 1 STZ- 19.1 +/- 2 nmol / gm。蛋白质）和DNA片段化（％对照-100 +/- 11 STZ- 330 + / -18）。与这些参数相比，谷胱甘肽过氧化物酶（酶水平U / g。蛋白质：对照431 +/- 19 STZ- 291 +/- 15）和SOD活性（对照414 +/- 9 STZ- 183 +/- 10）下降。在肾脏组织中。与抗氧化剂团队一起，抗死亡基因，Bcl-2和Bcl-XL蛋白的表达下降，线粒体敏感的促凋亡分子标记Cyt C水平显着增加。总而言之，这项研究表明，即使短期内由高血糖引起的氧化应激也可能干扰有利于细胞凋亡的组织生物化学，长期影响可能转化为严重的肾毒性后果。

著录项

  • 作者

    Shah, Krina A.;

  • 作者单位

    Long Island University, The Brooklyn Center.;

  • 授予单位 Long Island University, The Brooklyn Center.;
  • 学科 Health Sciences Toxicology.Health Sciences Pharmacology.
  • 学位 M.S.
  • 年度 2010
  • 页码 57 p.
  • 总页数 57
  • 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