Glucose-induced oxidative stress leads to in S-nitrosylation of protein disulfide isomerase in neuroblastoma cells
Glucose-induced oxidative stress leads to in S-nitrosylation of protein disulfide isomerase in neuroblastoma cells
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葡萄糖诱导的氧化应激导致神经母细胞瘤细胞中蛋白质二硫键异构酶的 S-亚硝基化
DOI：
10.1016/j.bbagen.2021.129998
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Mano Nariyasu
中科院分区：
文献类型：
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作者：
Ogura Jiro;Sugiura Hiroki;Tanaka Atsushi;Ono Shinji;Sato Toshiyuki;Sato Toshihiro;Maekawa Masamitsu;Yamaguchi Hiroaki;Mano Nariyasu
背景痴呆症给患者和护理人员带来了沉重的负担。由于糖尿病是痴呆症的危险因素，因此必须确定糖尿病和认知障碍之间的关系。蛋白质二硫键异构酶（PDI）是一种蛋白质氧化折叠酶。在阿尔茨海默病患者的脑组织中观察到PDIS-亚硝基化。本研究的目的是阐明PDIS-nitrosylation和diabetes.MethodsWe使用培养在高糖medium. ResultsSH-SY 5 Y细胞中的PDIS-nitrosylated水平增加7天，并保持高水平，直到28天在高糖medium. ResultsSH-SY 5 Y细胞之间的关系。使用表达PDI野生型或PDI C343 S的SH-SY 5 Y细胞，将PDI C343鉴定为葡萄糖诱导的S-亚硝基化的位点。在高糖培养基中培养的SH-SY 5 Y细胞中，IRE 1 α和PERK在第14天被磷酸化，并且磷酸化状态维持至第28天。为了确定S-亚硝基化PDI对内质网应激信号传导的影响，用S-亚硝基半胱氨酸（SNOC）处理SH-SY 5 Y细胞30 min，随后用无SNOC的培养基替换培养基，并培养细胞24 h。只有用SNOC处理的磷酸化IRE 1 α与PDIS-亚硝基化相关。新橙皮苷是柑橘类水果中的一种类黄酮，是一种天然抗氧化剂。结论葡萄糖负荷可导致PDIC 343的S-亚硝基化，并通过IRE 1 α磷酸化诱导神经元变性。
BackgroundDementia places a significant burden on both patients and caregivers. Since diabetes is a risk factor for dementia, it is imperative to identify the relationship between diabetes and cognitive disorders. Protein disulfide isomerase (PDI) is an enzyme for oxidative protein folding. PDIS-nitrosylation is observed in the brain tissues of Alzheimer's disease patients. The aim of this study is to clarify the relationship between PDIS-nitrosylation and diabetes.MethodsWe used SH-SY5Y cells cultured in high-glucose media.ResultsS-nitrosylated PDI level increased at 7 days and remained high till 28 days in SH-SY5Y cells cultured in high-glucose media. Using PDI wild-type- or PDI C343S-expressing SH-SY5Y cells, PDI C343 was identified as the site of glucose-inducedS-nitrosylation. IRE1α and PERK were phosphorylated at day 14 in the SH-SY5Y cells cultured in high-glucose media, and the phosphorylated status was maintained to day 28. To determine the effect ofS-nitrosylated PDI on endoplasmic reticulum stress signaling, SH-SY5Y cells were treated withS-nitrosocystein (SNOC) for 30 min, following which the medium was replaced with SNOC-free media and the cells were cultured for 24 h. Only phosphorylated IRE1α treated with SNOC was associated with PDIS-nitrosylation. Neohesperidin, a flavonoid in citrus fruits, is a natural antioxidant. The treatment with neohesperidin in the final 7 days of glucose loading reversed PDIS-nitrosylation and improved cell proliferation.ConclusionGlucose loading leads toS-nitrosylation of PDI C343 and induces neurodegeneration via IRE1α phosphorylation.General significanceThe results may be useful for designing curative treatment strategies for dementia.