Relationship of endothelin-1 and NLRP3 inflammasome activation in HT22 hippocampal cells in diabetes.
Relationship of endothelin-1 and NLRP3 inflammasome activation in HT22 hippocampal cells in diabetes.
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DOI：
10.1016/j.lfs.2016.02.043
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发表时间：
2016-08-15
期刊：
影响因子：
6.1
通讯作者：
Ergul A
中科院分区：
文献类型：
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作者：
Ward R;Ergul A
糖尿病增加了这种风险，并加剧了认知能力下降的进程。糖尿病大鼠使用双重内皮素受体拮抗剂波生坦治疗，已被证明可以改善基于海马区的认知障碍。NLRP3炎症小体与糖尿病的血管并发症有关。我们假设糖尿病引起的海马细胞内皮素-1(ET-1)的增加导致NLRP3的激活和炎症。体外培养的HT2 2细胞暴露于正常(2 5 MM)、低(5.5 mM)和高(5 0 MM)葡萄糖条件下，分别加入和不加入棕榈酸酯(2 0 0μM)，分别加入和不加入10μM波生坦2 4h。用蛋白印迹法检测NLRP3的活性。用双抗体夹心法检测ET-1和IL-1β的表达。HT22细胞在正常条件下合成高水平的ET-1，而在棕榈酸酯和波生坦以及低糖和高糖条件下，ET-1的合成被减少。在正常血糖中，ET-1水平降低与NLRP3和IL-1β的激活程度增加有关。与正常和低糖相比，高糖增加了NLRP3标志物和激活。这些数据表明，ET-1可能对神经元具有保护作用。尽管内皮素拮抗剂可能有益于改善血管功能障碍和认知功能障碍，但其对海马神经元的影响仍需进一步探讨。
Diabetes increases the risk and worsens the progression of cognitive decline. Diabetic rats treated with the dual endothelin receptor antagonist bosentan, have been shown to improve hippocampal-based cognitive deficits. The NLRP3 inflammasome has been implicated in vascular complications of diabetes. We hypothesized that diabetes-mediated increase in endothelin-1 (ET-1) in hippocampal cells causes NLRP3 activation and inflammation. An in vitro model was employed by exposing HT22 hippocampal cells to normal (25 mM), low (5.5 mM) and high (50 mM) glucose conditions with and without palmitate (200 μM) in the presence and absence of 10 μM bosentan for 24 hours. NLRP3 activity was measured by western blotting for cryopyrin and caspase-1. ET-1 and IL-1β expression was determined by ELISA. HT22 cells synthesize high levels of ET-1 in normal conditions, which was reduced with palmitate and bosentan as well as low and high glucose conditions. Decreased ET-1 levels were associated with greater activation of NLRP3 and IL-1β in normal glucose. High glucose increased NLRP3 markers and activation compared to normal and low glucose. These data suggest that ET-1 may be protective to neurons. Although endothelin antagonism may be beneficial in improving vascular dysfunction and cognitive impairment, its impact on hippocampal neurons should be further explored.