Naturally occurring rare sugars are free radical scavengers and can ameliorate endoplasmic reticulum stress.
Naturally occurring rare sugars are free radical scavengers and can ameliorate endoplasmic reticulum stress.
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天然存在的稀有糖是自由基清除剂，可以改善内质网应激。
DOI：
10.1024/0300-9831/a000517
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Tokuda M.
中科院分区：
文献类型：
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作者：
Mooradian AD;Haas MJ;Onstead-Haas L;Tani Y;Iida T;Tokuda M.
由于天然稀有糖作为甜味剂的潜在用途，我们在人冠状动脉内皮细胞中研究了它们对超氧化物（SO）、羟基和过氧自由基以及内质网（ER）应激的影响。采用超氧反应探针2-甲基-6-（4-甲氧基苯基）- 3,7 -二氢咪唑[1,2 - a]吡嗪-3- 1盐酸盐化学发光法测定SO的生成。植红蛋白荧光法用于监测在羟基或过氧基自由基生成剂[cuso4和偶氮（2 -氨基丙烷）盐酸]存在下糖的清除活性。测量以相对光单位（RLU）进行。采用内质网应激敏感分泌碱性磷酸酶（SAP）测定法和Western blot分析未折叠蛋白反应中关键蛋白CHOP47、eIF2α和JNK1的表达和磷酸化情况。d -葡萄糖（27.5 mM）增加了SO生成（对照组为5536±283 RLU，对照组为2963±205 RLU， p< 0.0007），减少了SAP分泌（对照组为73411±3971 RLU，对照组为101749±7652 RLU， p< 0.005），提示内质膜应激。用5.5或27.5 mM的D-allulose、D-allose、d - sorose和D-tagatose处理细胞可减少SO生成（均p< 0.05）。这不能归因于被测试的稀有糖抑制了细胞对葡萄糖的摄取。在无细胞系统中，与葡萄糖相比，这四种稀有糖具有显著更高的SO、羟基和过氧自由基清除活性（均p< 0.01）。用稀有糖处理细胞可减少内质网应激。然而，与其他三种稀有糖不同，d -山梨糖不抑制tunicamy霉素诱导的eIF2α磷酸化。天然存在的稀有糖是自由基清除剂，可以减少内质网应激。
Because of potential use of naturally occurring rare sugars as sweeteners, their effect on superoxide (SO), hydroxyl and peroxyl radicals and endoplasmic reticulum (ER) stress was examined in human coronary artery endothelial cells. SO generation was measured using the superoxide-reactive probe 2-methyl-6-(4-methoxyphenyl)-3, 7-dihydroimidazo [1, 2-A] pyrazin-3-one hydrochloride chemiluminescence. Phycoerythrin fluorescence based assay was used to monitor scavenging activity of sugars in the presence of hydroxyl or peroxyl radical generators [CuSO 4 and azobis (2 amidinopropane) hydrochloride respectively]. Measurements were made in relative light units (RLU). ER stress was measured with an ER stress-sensitive secreted alkaline phosphatase (SAP) assay and by Western blot analysis of the expression and phosphorylation of key proteins in the unfolded protein response, namely CHOP47, eIF2α and JNK1. D-Glucose (27.5 mM) increased SO generation (5536±283 vs. 2963±205 RLU in controls; p< 0.0007) and decreased SAP secretion (73411±3971 vs. 101749±7652 RLU in controls; p< 0.005) indicating ER stress. Treatment of cells with 5.5 or 27.5 mM of D-allulose, D-allose, D-sorbose and D-tagatose reduced SO generation (all p< 0.05). This could not be attributed to inhibition of cellular uptake of dextrose by the rare sugars tested. In a cell free system, all four rare sugars had significantly more SO, hydroxyl and peroxyl radical scavenging activity compared to dextrose (all p< 0.01). Treatment of cells with rare sugars reduced ER stress. However, unlike other three rare sugars, D-sorbose did not inhibit tunicamycin-induced eIF2α phosphorylation. Naturally occurring rare sugars are free radical scavengers and can reduce ER stress.