Procyanidin B2 mitigates endothelial endoplasmic reticulum stress through a PPARδ-Dependent mechanism.
Procyanidin B2 mitigates endothelial endoplasmic reticulum stress through a PPARδ-Dependent mechanism.
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原花青素 B2 通过 PPAR δ 依赖性机制减轻内皮内质网应激
DOI：
10.1016/j.redox.2020.101728
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发表时间：
2020-10
期刊：
影响因子：
11.4
通讯作者：
Wang N
中科院分区：
文献类型：
--
作者：
Nie X;Tang W;Zhang Z;Yang C;Qian L;Xie X;Qiang E;Zhao J;Zhao W;Xiao L;Wang N
高血糖诱导的内皮内质网(ER)应激参与糖尿病及其血管并发症的病理生理过程。原花青素在许多植物食品中含量丰富，已被证明对糖尿病、心血管疾病和其他代谢性疾病具有多种有益作用。在本研究中，我们研究了分布最广泛的天然原花青素原花青素B2(PCB2)对高糖诱导的内皮细胞内质网应激的影响及其机制。我们发现PCB2可以缓解高糖激活的人血管内皮细胞内质网应激途径(PERK、IRE1、α和ATF6)。此外，我们还发现PCB2通过激活过氧化物酶体增殖物激活受体δ(PPARδ)来减轻内皮细胞内质网应激。我们证明了PCB2直接与PPARδ结合并激活。相反，选择性PPARδ拮抗剂GSK0660可减弱PCB2对内质网应激信号通路的抑制作用。从功能上讲，PCB2改善了高糖损伤的小鼠主动脉内皮依赖的松弛。预先用GSK0660或EC特异性PPARδ基因敲除小鼠的主动脉，PCB2对血管扩张的保护作用被取消。此外，多氯联苯对内质网应激和内皮功能障碍的保护作用需要PPARδ和AMPK的相互依赖作用。总而言之，我们证明了PCB2除了作为自由基清除剂的经典作用外，还通过PPARδ介导的机制缓解内质网应激和改善血管扩张。这些发现进一步强调了原花青素在干预内质网应激和与内皮功能障碍相关的代谢紊乱方面的新作用。PCB2是一种富含水果和蔬菜的多酚，可以缓解高糖诱导的内皮细胞内质网应激。PCB2结合并激活核受体PPARδ，后者通过AMPK抑制内质网应激。PCB2改善高糖损伤的内皮依赖性血管松弛。
Hyperglycemia-induced endothelial endoplasmic reticulum (ER) stress is implicated in the pathophysiology of diabetes and its vascular complications. Procyanidins are enriched in many plant foods and have been demonstrated to exert several beneficial effects on diabetes, cardiovascular and other metabolic diseases. In the present study, we investigated the effect of procyanidin B2 (PCB2), the most widely distributed natural procyanidin, on ER stress evoked by high glucose in endothelial cells (ECs) and the underlying mechanisms. We showed that PCB2 mitigated the high glucose-activated ER stress pathways (PERK, IRE1α and ATF6) in human vascular ECs. In addition, we found that PCB2 attenuated endothelial ER stress via the activation of peroxisome proliferator-activated receptor δ (PPARδ). We demonstrated that PCB2 directly bound to and activated PPARδ. Conversely, GSK0660, a selective PPARδ antagonist, attenuated the suppressive effect of PCB2 on the ER stress signal pathway. Functionally, PCB2 ameliorated the high glucose-impaired endothelium-dependent relaxation in mouse aortas. The protective effect of PCB2 on vasodilation was abolished in the aortas pretreated with GSK0660 or those from the EC-specific PPARδ knockout mice. Moreover, the protective effects of PCB2 on ER stress and endothelial dysfunction required the inter-dependent actions of PPARδ and AMPK. Collectively, we demonstrated that PCB2 mitigated ER stress and ameliorated vasodilation via a PPARδ-mediated mechanism beyond its classic action as a scavenger of free radicals. These findings further highlighted the novel roles of procyanidins in intervening the ER stress and metabolic disorders related to endothelial dysfunction. PCB2, a polyphenol enriched in fruits and vegetables, mitigates high glucose-induced ER stress in endothelium.. PCB2 binds to and activates nuclear receptor PPARδ, which acts through AMPK to repress ER stress. PCB2 ameliorates high glucose-impaired endothelium-dependent vasorelaxation.
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影响因子：
64.8
作者：
Corder, R.;Mullen, W.;Crozier, A.
通讯作者：
Crozier, A.
DOI：
10.1007/978-1-59745-523-7_20
发表时间：
2009
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
通讯作者：
--
影响因子：
39.3
作者：
Crowe, Francesca L.;Roddam, Andrew W.;Riboli, Elio
通讯作者：
Riboli, Elio
DOI：
10.1016/j.bbadis.2014.07.002
发表时间：
2014-09
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Li H;Min Q;Ouyang C;Lee J;He C;Zou MH;Xie Z
通讯作者：
Xie Z
影响因子：
7.1
作者：
Holt, RR;Lazarus, SA;Keen, CL
通讯作者：
Keen, CL