• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American Journal of Physiology >Accumulation of nonesterified fatty acids causes the sustained energetic deficit in kidney proximal tubules after hypoxia-reoxygenation.
【24h】

Accumulation of nonesterified fatty acids causes the sustained energetic deficit in kidney proximal tubules after hypoxia-reoxygenation.

机译：缺氧-复氧后，未酯化脂肪酸的积累会导致肾近端小管持续的能量缺乏。

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

Kidney proximal tubules exhibit decreased ATP and reduced, but not absent, mitochondrial membrane potential (Deltapsi(m)) during reoxygenation after severe hypoxia. This energetic deficit, which plays a pivotal role in overall cellular recovery, cannot be explained by loss of mitochondrial membrane integrity, decreased electron transport, or compromised F1F0-ATPase and adenine nucleotide translocase activities. Addition of oleate to permeabilized tubules produced concentration-dependent decreases of Deltapsi(m) measured by safranin O uptake (threshold for oleate = 0.25 microM, 1.6 nmol/mg protein; maximal effect = 4 microM, 26 nmol/mg) that were reversed by delipidated BSA (dBSA). Cell nonesterified fatty acid (NEFA) levels increased from <1 to 17.4 nmol/mg protein during 60- min hypoxia and remained elevated at 7.6 nmol/mg after 60 min reoxygenation, at which time ATP had recovered to only 10% of control values. Safranin O uptake in reoxygenated tubules, which was decreased 85% after 60-min hypoxia, was normalized by dBSA, which improved ATP synthesis as well. dBSA also almost completely normalized Deltapsi(m) when the duration of hypoxia was increased to 120 min. In intact tubules, the protective substrate combination of alpha-ketoglutarate + malate (alpha-KG/MAL) increased ATP three- to fourfold, limited NEFA accumulation during hypoxia by 50%, and lowered NEFA during reoxygenation. Notably, dBSA also improved ATP recovery when added to intact tubules during reoxygenation and was additive to the effect of alpha-KG/MAL. We conclude that NEFA overload is the primary cause of energetic failure of reoxygenated proximal tubules and lowering NEFA substantially contributes to the benefit from supplementation with alpha-KG/MAL.
机译：在严重缺氧后的复氧过程中，肾脏近端肾小管的ATP降低，线粒体膜电位（Deltapsi（m））降低，但不降低。这种能量不足在整个细胞的恢复中起着举足轻重的作用，不能用线粒体膜完整性的丧失，电子传递的减少或F1F0-ATPase和腺嘌呤核苷酸转位酶活性的降低来解释。将油酸盐添加到通透的小管中，通过藏红素O的摄取（油酸盐的阈值= 0.25 microM，1.6 nmol / mg蛋白;最大作用= 4 microM，26 nmol / mg）测量，浓度依赖性的Deltapsi（m）降低。脱脂BSA（dBSA）。在缺氧60分钟时，细胞非酯化脂肪酸（NEFA）的水平从<1增加到17.4 nmol / mg蛋白质，在再充氧60分钟后仍保持在7.6 nmol / mg的水平，此时ATP已恢复至对照值的10％。氧合小管中的番红花O吸收（缺氧60分钟后降低了85％）通过dBSA进行了标准化，这也改善了ATP的合成。当缺氧持续时间增加到120分钟时，dBSA也几乎完全标准化了Deltapsi（m）。在完整的肾小管中，α-酮戊二酸+苹果酸（α-KG/ MAL）的保护性底物组合使ATP升高三至四倍，缺氧时NEFA积累受到限制，降低了50％，并在复氧时降低了NEFA。值得注意的是，在复氧过程中将dBSA添加至完整的小管时，dBSA还可以提高ATP的回收率，并且可以增强α-KG/ MAL的作用。我们得出结论，NEFA超负荷是再充氧的近端小管能量衰竭的主要原因，而降低NEFA实质上有助于补充α-KG/ MAL。

著录项

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