Fisetin lowers methylglyoxal dependent protein glycation and limits the complications of diabetes.
Fisetin lowers methylglyoxal dependent protein glycation and limits the complications of diabetes.
复制标题
DOI：
10.1371/journal.pone.0021226
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Schubert D
中科院分区：
文献类型：
--
作者：
Maher P;Dargusch R;Ehren JL;Okada S;Sharma K;Schubert D
由反应性二羰基和α-乙醛甲基乙二醛（MG）引起的大分子糖基化升高与糖尿病及其并发症有关。我们已经确定了一种罕见的黄酮，非瑟酮，它增加了谷胱甘肽酶1的水平和活性，该酶是去除MG所需的酶，以及其必需的辅因子谷胱甘肽的合成。显示非瑟酮减少秋田小鼠（1型糖尿病模型）中糖尿病的两种主要并发症。虽然非瑟酮对血糖升高没有影响，但它减少了肾脏肥大和蛋白尿，并在旷场试验中保持了正常的运动水平。这与非瑟酮给药动物的血液、肾脏和脑中MG糖化蛋白的减少相关，沿着的是谷胱甘肽1酶活性的增加和谷胱甘肽合成限速酶（谷胱甘肽1的辅助因子）表达的升高。晚期糖基化终产物受体（AGEs）、血清淀粉样蛋白A和血清C-反应蛋白（蛋白氧化、糖基化和炎症的标志物）的表达在糖尿病秋田小鼠中也增加，而非瑟酮降低。它的结论是，非瑟酮降低与糖尿病相关的MG-蛋白糖基化的升高，并改善多种并发症的疾病。因此，非瑟酮或合成衍生物可能具有治疗糖尿病并发症的潜在治疗用途。
The elevated glycation of macromolecules by the reactive dicarbonyl and α-oxoaldehyde methylglyoxal (MG) has been associated with diabetes and its complications. We have identified a rare flavone, fisetin, which increases the level and activity of glyoxalase 1, the enzyme required for the removal of MG, as well as the synthesis of its essential co-factor, glutathione. It is shown that fisetin reduces two major complications of diabetes in Akita mice, a model of type 1 diabetes. Although fisetin had no effect on the elevation of blood sugar, it reduced kidney hypertrophy and albuminuria and maintained normal levels of locomotion in the open field test. This correlated with a reduction in proteins glycated by MG in the blood, kidney and brain of fisetin-treated animals along with an increase in glyoxalase 1 enzyme activity and an elevation in the expression of the rate-limiting enzyme for the synthesis of glutathione, a co-factor for glyoxalase 1. The expression of the receptor for advanced glycation end products (RAGE), serum amyloid A and serum C-reactive protein, markers of protein oxidation, glycation and inflammation, were also increased in diabetic Akita mice and reduced by fisetin. It is concluded that fisetin lowers the elevation of MG-protein glycation that is associated with diabetes and ameliorates multiple complications of the disease. Therefore, fisetin or a synthetic derivative may have potential therapeutic use for the treatment of diabetic complications.
登录
查看更多内容
影响因子：
4.3
作者：
King, George L.
通讯作者：
King, George L.
影响因子：
4.2
作者：
Burdo, Joseph R.;Chen, Qi;Schubert, David
通讯作者：
Schubert, David
影响因子：
2.9
作者：
Maher, Pamela;Salgado, Karmen F.;Lapchak, Paul A.
通讯作者：
Lapchak, Paul A.
影响因子：
19.6
作者：
MACKAY, K;STRIKER, LJ;STRIKER, GE
通讯作者：
STRIKER, GE
影响因子：
8.2
作者：
Jacobson, A. M.;Ryan, C. M.;Cleary, P. A.;Waberski, B. H.;Weinger, K.;Musen, G.;Dahms, W.
通讯作者：
Dahms, W.