Multi-targeted mechanisms underlying the endothelial protective effects of the diabetic-safe sweetener erythritol.
Multi-targeted mechanisms underlying the endothelial protective effects of the diabetic-safe sweetener erythritol.
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DOI：
10.1371/journal.pone.0065741
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Bast A
中科院分区：
文献类型：
--
作者：
Boesten DM;Berger A;de Cock P;Dong H;Hammock BD;den Hartog GJ;Bast A
糖尿病的特征是高血糖和血管病理学的发展。内皮细胞功能障碍是糖尿病血管并发症发病机制的起点。我们之前证明多元醇赤藓糖醇是一种羟基自由基清除剂，可预防糖尿病大鼠内皮细胞功能障碍的发生。为了揭示赤藓糖醇介导这种保护作用的机制（除了清除自由基之外），我们使用靶向和转录组学方法评估了赤藓糖醇对暴露于正常（7 mM）和高葡萄糖（30 mM）或糖尿病应激源（例如 SIN-1）的内皮细胞的影响。这项研究表明赤藓糖醇（即在非糖尿病条件下）对内皮细胞的影响最小。然而，在高血糖条件下，赤藓糖醇可以保护内皮细胞免受糖尿病应激源（即高葡萄糖和过氧亚硝酸盐）诱导的细胞死亡。高血糖还会引起许多有害影响，例如一氧化氮释放增加，则相反。此外，总转录组分析表明，由于高葡萄糖而受到差异调节的生物过程可以被赤藓糖醇纠正。我们得出的结论是，赤藓糖醇在高葡萄糖条件下通过对多个靶标的影响来保护内皮细胞。总体而言，这些数据表明赤藓糖醇在高血糖条件下具有治疗上重要的内皮保护作用。
Diabetes is characterized by hyperglycemia and development of vascular pathology. Endothelial cell dysfunction is a starting point for pathogenesis of vascular complications in diabetes. We previously showed the polyol erythritol to be a hydroxyl radical scavenger preventing endothelial cell dysfunction onset in diabetic rats. To unravel mechanisms, other than scavenging of radicals, by which erythritol mediates this protective effect, we evaluated effects of erythritol in endothelial cells exposed to normal (7 mM) and high glucose (30 mM) or diabetic stressors (e.g. SIN-1) using targeted and transcriptomic approaches. This study demonstrates that erythritol (i.e. under non-diabetic conditions) has minimal effects on endothelial cells. However, under hyperglycemic conditions erythritol protected endothelial cells against cell death induced by diabetic stressors (i.e. high glucose and peroxynitrite). Also a number of harmful effects caused by high glucose, e.g. increased nitric oxide release, are reversed. Additionally, total transcriptome analysis indicated that biological processes which are differentially regulated due to high glucose are corrected by erythritol. We conclude that erythritol protects endothelial cells during high glucose conditions via effects on multiple targets. Overall, these data indicate a therapeutically important endothelial protective effect of erythritol under hyperglycemic conditions.
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影响因子：
13.6
作者：
Dobrian, Anca D.;Lieb, David C.;Cole, Banumathi K.;Taylor-Fishwick, David A.;Chakrabarti, Swarup K.;Nadler, Jerry L.
通讯作者：
Nadler, Jerry L.
影响因子：
9.3
作者：
Kageyama S;Yokoo H;Tomita K;Kageyama-Yahara N;Uchimido R;Matsuda N;Yamamoto S;Hattori Y
通讯作者：
Hattori Y
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
3.8
作者：
Chen, JQ;Li, YB;Yager, JD
通讯作者：
Yager, JD
影响因子：
2.1
作者：
Irizarry, RA;Hobbs, B;Speed, TP
通讯作者：
Speed, TP