ALA/LA ameliorates glucose toxicity on HK-2 cells by attenuating oxidative stress and apoptosis through the ROS/p38/TGF-β(1) pathway.
ALA/LA ameliorates glucose toxicity on HK-2 cells by attenuating oxidative stress and apoptosis through the ROS/p38/TGF-β(1) pathway.
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ALA/LA 通过 ROS/p38/TGF-beta(1) 途径减轻氧化应激和细胞凋亡，从而改善 HK-2 细胞的葡萄糖毒性
DOI：
10.1186/s12944-017-0611-6
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发表时间：
2017-11-16
影响因子：
4.5
通讯作者：
Zhai C
中科院分区：
文献类型：
--
作者：
Jiang M;Zhang H;Zhai L;Ye B;Cheng Y;Zhai C
越来越多的证据表明，氧化应激（OS）在糖尿病肾病（DN）中起着关键作用。在先前的研究中，我们证明了ALA/LA保护HK-2细胞免受高糖诱导的细胞毒性。本研究旨在建立HK-2细胞葡萄糖损伤模型，探讨ALA/LA对高糖诱导的HK-2细胞TGF-β1过度分泌的保护作用及其可能的机制。ALA/LA处理高糖诱导的HK-2细胞中OS标志物的表达，采用ELISA和流式细胞仪检测细胞抗氧化酶活性和活性氧（ROS）的产生，以及细胞凋亡率。采用实时荧光定量RT-PCR和western blot检测p38/转化生长因子β1（TGF-β1）信号通路的变化。葡萄糖对HK-2细胞毒性的建模条件为葡萄糖浓度为40.9mM。ALA/LA能显著提高葡萄糖诱导的抗氧化酶活性，降低高糖诱导的ROS产生。本研究还发现ALA/LA通过ROS/p38通路降低高糖应激下HK-2细胞的凋亡率和TGF-β1水平。ALA/LA通过抑制HK-2细胞内ROS的产生、下调p38 MAPK通路的激活和TGF-β1的表达而发挥保护作用。
Growing evidence indicates that oxidative stress (OS) plays a pivotal role in Diabetic nephropathy (DN). In a previous study we demonstrated that ALA/LA protected HK-2 cells against high glucose-induced cytotoxicity. So we aimed to establish the glucose injury model of HK-2 cells and investigate the beneficial effects of ALA/LA on high glucose-induced excessive production of TGF-β1 and the possible mechanisms mediating the effects. The expression of OS markers in high glucose-induced HK-2 cells treated with ALA/LA., including the antioxidant enzymes and reactive oxygen species (ROS) production, as well as the apoptosis rate were assayed by ELISA and flow cytometry. The p38/transforming growth factor β1 (TGF-β1) signal pathway were measured by real-time RT-PCR and western blot. The modeling condition of glucose toxicity on HK-2 cells was at the glucose concentration of 40.9 mM. ALA/LA can significantly increase the activities of antioxidant enzymes and decrease ROS production stimulated by high glucose. The study also found that ALA/LA caused a decrease in the apoptosis rate and TGF-β1 level of HK-2 cells under high glucose stress through the ROS/p38 pathway. ALA/LA exerts protective effects in vitro through inhibition of ROS generation, down regulation of the activation of the p38MAPK pathway and the expression of TGF-β1 in HK-2 cells.
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影响因子：
19.6
作者：
KREISBERG, JI;GARONI, JA;AYO, SH
通讯作者：
AYO, SH
影响因子：
3.1
作者：
Lauretani F;Maggio M;Pizzarelli F;Michelassi S;Ruggiero C;Ceda GP;Bandinelli S;Ferrucci L
通讯作者：
Ferrucci L
DOI：
10.1152/ajprenal.2001.280.3.f495
发表时间：
2001-03-01
影响因子：
4.2
作者：
Chin, BY;Mohsenin, A;Choi, ME
通讯作者：
Choi, ME
DOI：
10.1016/s0027-5107(03)00134-9
发表时间：
2003-09-29
影响因子：
2.3
作者：
Beeharry, N;Lowe, JE;Green, IC
通讯作者：
Green, IC
影响因子：
5.6
作者：
Dasilva, Gabriel;Pazos, Manuel;Medina, Isabel
通讯作者：
Medina, Isabel