Induction of endoplasmic reticulum stress in retinal pericytes by glucose deprivation
Induction of endoplasmic reticulum stress in retinal pericytes by glucose deprivation
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DOI：
10.1080/02713680600966785
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发表时间：
2006-11-01
影响因子：
2
通讯作者：
Shinohara, Toshimichi
中科院分区：
文献类型：
--
作者：
Ikesugi, Kengo;Mulhern, Michael L.;Shinohara, Toshimichi
糖尿病视网膜病变是与糖尿病相关的主要微血管并发症之一，视网膜毛细血管周细胞的选择性变性被认为是早期视网膜病变的标志。由于葡萄糖波动通常发生在糖尿病中，我们假设这些波动会增加内质网（ER）应激并诱导视网膜周细胞中的未折叠蛋白反应（UPR）。为了研究是否可以在视网膜周细胞中诱导ER应激和UPR，在不同浓度的葡萄糖中培养大鼠视网膜毛细血管周细胞。研究发现，低血糖而非高血糖会激活周细胞中的 UPR 特异性酶。当周细胞在葡萄糖浓度从高葡萄糖降低到低葡萄糖或无葡萄糖的条件下培养时，也观察到强烈的 UPR 激活导致细胞凋亡。这些结果表明UPR的诱导不仅与绝对浓度有关，而且与从较高浓度到较低浓度的葡萄糖的转变有关。
Diabetic retinopathy is one of the major microvascular complications associated with diabetes mellitus, and the selective degeneration of retinal capillary pericytes is considered to be a hallmark of early retinopathy. Because glucose fluctuations commonly occur in diabetes, we hypothesized that these fluctuations will increase the endoplasmic reticulum (ER) stress and induce the unfolded protein response (UPR) in retinal pericytes. To study whether ER stress and the UPR can be induced in retinal pericytes, rat retinal capillary pericytes were cultured in different concentrations of glucose. Hypoglycemia but not hyperglycemia was found to activate UPR-specific enzymes in pericytes. Strong UPR activation leading to apoptosis was also observed when pericytes were cultured in glucose concentrations that were reduced from high to low or no glucose. These results indicate that induction of UPR is related not only to absolute concentrations but also to a shifting from higher to lower concentrations of glucose.