Reduced endoplasmic reticulum luminal calcium links saturated fatty acid-mediated endoplasmic reticulum stress and cell death in liver cells.
Reduced endoplasmic reticulum luminal calcium links saturated fatty acid-mediated endoplasmic reticulum stress and cell death in liver cells.
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DOI：
10.1007/s11010-009-0142-1
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发表时间：
2009-11
影响因子：
4.3
通讯作者：
Pagliassotti, Michael J.
中科院分区：
文献类型：
--
作者：
Wei, Yuren;Wang, Dong;Gentile, Christopher L.;Pagliassotti, Michael J.
长期暴露于升高的游离脂肪酸，特别是长链饱和脂肪酸，在许多细胞类型中引起内质网（ER）应激和细胞死亡。尚未确定引起ER应激和未折叠蛋白响应于肝细胞中脂肪酸而活化的ER的扰动。本研究采用H4 IIE肝细胞和原代大鼠肝细胞来研究饱和脂肪酸通过影响内质网腔钙储备诱导内质网应激的假设。H4 IIE肝细胞和原代肝细胞暴露于棕榈酸酯和硬脂酸酯在相似的时间过程（6小时）内减少了对毒胡萝卜素敏感的钙储存和ER应激的生化标志物。这些变化发生在细胞死亡之前，仅在稍后的时间点（16 h）观察到。与油酸酯共孵育防止了响应于棕榈酸酯观察到的钙储存的减少、ER应激标志物的诱导和细胞死亡。包括钙螯合剂，BAPTA-AM或EGTA，减少棕榈酸和硬脂酸介导的富集细胞色素c后线粒体上清液馏分和细胞死亡。这些数据表明，内质网腔钙的重新分布有助于长链饱和脂肪酸介导的内质网应激和细胞死亡。
Chronic exposure to elevated free fatty acids, in particular long chain saturated fatty acids, provokes endoplasmic reticulum (ER) stress and cell death in a number of cell types. The perturbations to the ER that instigate ER stress and activation of the unfolded protein in response to fatty acids in hepatocytes have not been identified. The present study employed H4IIE liver cells and primary rat hepatocytes to examine the hypothesis that saturated fatty acids induce ER stress via effects on ER luminal calcium stores. Exposure of H4IIE liver cells and primary hepatocytes to palmitate and stearate reduced thapsigargin-sensitive calcium stores and biochemical markers of ER stress over similar time courses (6h). These changes preceded cell death, which was only observed at later time points (16h). Co-incubation with oleate prevented the reduction in calcium stores, induction of ER stress markers and cell death observed in response to palmitate. Inclusion of calcium chelators, BAPTA-AM or EGTA, reduced palmitate- and stearate-mediated enrichment of cytochrome c in post-mitochondrial supernatant fractions and cell death. These data suggest that redistribution of ER luminal calcium contributes to long chain saturated fatty acid-mediated ER stress and cell death.
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影响因子：
4.8
作者：
Listenberger, LL;Ory, DS;Schaffer, JE
通讯作者：
Schaffer, JE
影响因子：
3.1
作者：
Nehra, V;Angulo, P;Lindor, KD
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Lindor, KD
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13.5
作者：
Feldstein, AE;Werneburg, NW;Gores, GJ
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Gores, GJ
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4.8
作者：
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Gores, Gregory J.
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6.5
作者：
Borradaile, Nica M.;Han, Xianlin;Schaffer, Jean E.
通讯作者：
Schaffer, Jean E.