Tyrosol, an olive oil polyphenol, inhibits ER stress-induced apoptosis in pancreatic β-cell through JNK signaling
Tyrosol, an olive oil polyphenol, inhibits ER stress-induced apoptosis in pancreatic β-cell through JNK signaling
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DOI：
10.1016/j.bbrc.2015.12.036
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发表时间：
2016-01-15
影响因子：
3.1
通讯作者：
Ahn, Jiyun
中科院分区：
文献类型：
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作者：
Lee, Hyunjung;Im, Sung Won;Ahn, Jiyun
胰腺β细胞功能障碍是2型糖尿病发生的主要决定因素。由于代谢综合征中胰岛素分泌受到刺激，内质网应激在β细胞衰竭中起着重要的调节作用。在这项研究中，我们研究了一种抗氧化剂酚类化合物，酪醇是否能保护内质网应激相关的β细胞功能障碍。为了解决这个问题，我们将胰腺β细胞NIT-1与酪醇一起暴露在tunicamycin中。我们发现tyrosol以剂量依赖的方式减少了tunicamycin诱导的细胞死亡。我们还检测到酪醇降低了细胞凋亡相关标志物的表达。tunicamycin暴露可引起UPR反应，tyrosol共处理可减少内质网应激。酪醇的这些作用是通过JNK的磷酸化介导的。此外，我们证实补充酪醇可以改善高脂肪喂养引起的β细胞损失。综上所述，我们的研究为酪醇对内质网应激诱导的β细胞死亡的保护作用的信号转导提供了分子基础。因此，我们认为酪醇可能是一种潜在的治疗2型糖尿病的候选药物。(C) 2015爱思唯尔公司版权所有。
Dysfunction of pancreatic beta-cell is a major determinant for the development of type 2 diabetes. Because of the stimulated insulin secretion in metabolic syndrome, endoplasmic reticulum (ER) stress plays a central mediator for beta-cell failure. In this study, we investigated whether an antioxidant phenolic compound, tyrosol protects against beta-cell dysfunction associated with ER stress. To address this issue, we exposed pancreatic beta cells, NIT-1 to tunicamycin with tyrosol. We found tyrosol diminished tunicamycin-induced cell death in a dose-dependent manner. We also detected tyrosol decreased the expressions of apoptosis-related markers. Exposure to tunicamycin evoked UPR response and co-treatment of tyrosol led to reduction of ER stress. These effects of tyrosol were mediated by the phosphorylation of JNK. Moreover, we confirmed supplement of tyrosol ameliorated beta-cell loss induced by high fat feeding. Taken together, our study provides a molecular basis for signaling transduction of protective effect of tyrosol against ER stress-induced beta-cell death. Therefore, we suggest tyrosol could be a potential therapeutic candidate for amelioration of type 2 diabetes. (C) 2015 Elsevier Inc. All rights reserved.