Effects of Vitamin B(12) Deficiency on Amyloid-β Toxicity in Caenorhabditis elegans.
Effects of Vitamin B(12) Deficiency on Amyloid-β Toxicity in Caenorhabditis elegans.
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DOI：
10.3390/antiox10060962
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发表时间：
2021-06-15
期刊：
影响因子：
--
通讯作者：
Yabuta Y
中科院分区：
文献类型：
--
作者：
Andra A;Tanigawa S;Bito T;Ishihara A;Watanabe F;Yabuta Y
高同型半胱氨酸（Hcy）水平，主要是由维生素B12缺乏引起的，已报道可诱导阿尔茨海默病小鼠模型中淀粉样蛋白-β（Aβ）形成和tau蛋白过度磷酸化。然而，B12缺乏和Aβ聚集之间的关系以及相关机制知之甚少。在本研究中，我们使用转基因C。elegans菌株GMC 101，其在肌肉细胞中表达人Aβ1-42肽，以研究B12缺乏对Aβ聚集相关麻痹的影响。C.线虫GMC 101在线虫生长培养基上生长，其中添加或不添加B12或添加2-O-α-D-吡喃葡萄糖基-L-抗坏血酸（阿萨-2G）。通过次氯酸盐漂白使蠕虫年龄同步，并在20 °C下孵育。在蠕虫达到幼成虫阶段后，将温度升高至25 °C以诱导Aβ产生。缺乏B12补充剂的蠕虫表现出更快和更严重的麻痹比那些收到它。此外，补充B12缺乏的生长培养基与阿萨-2G拯救麻痹表型。而阿萨-2G对Aβ肽的聚集无影响。我们的研究结果表明，补充B12降低了Hcy水平，减轻了Aβ毒性，表明Hcy水平升高引起的氧化应激是Aβ毒性的重要因素。
High homocysteine (Hcy) levels, mainly caused by vitamin B12 deficiency, have been reported to induce amyloid-β (Aβ) formation and tau hyperphosphorylation in mouse models of Alzheimer’s disease. However, the relationship between B12 deficiency and Aβ aggregation is poorly understood, as is the associated mechanism. In the current study, we used the transgenic C. elegans strain GMC101, which expresses human Aβ1–42 peptides in muscle cells, to investigate the effects of B12 deficiency on Aβ aggregation–associated paralysis. C. elegans GMC101 was grown on nematode growth medium with or without B12 supplementation or with 2-O-α-D-glucopyranosyl-L-ascorbic acid (AsA-2G) supplementation. The worms were age-synchronized by hypochlorite bleaching and incubated at 20 °C. After the worms reached the young adult stage, the temperature was increased to 25 °C to induce Aβ production. Worms lacking B12 supplementation exhibited paralysis faster and more severely than those that received it. Furthermore, supplementing B12-deficient growth medium with AsA-2G rescued the paralysis phenotype. However, AsA-2G had no effect on the aggregation of Aβ peptides. Our results indicated that B12 supplementation lowered Hcy levels and alleviated Aβ toxicity, suggesting that oxidative stress caused by elevated Hcy levels is an important factor in Aβ toxicity.
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影响因子：
11.2
作者：
Li, Jian-Guo;Chu, Jin;Barrero, Carlos;Merali, Salim;Pratico, Domenico
通讯作者：
Pratico, Domenico
影响因子：
64.5
作者：
Watson E;MacNeil LT;Ritter AD;Yilmaz LS;Rosebrock AP;Caudy AA;Walhout AJ
通讯作者：
Walhout AJ
影响因子：
4.1
作者：
Siow, Yaw L.;Au-Yeung, Kathy K. W.;O, Karmin
通讯作者：
O, Karmin
DOI：
10.1111/j.1532-5415.1996.tb01866.x
发表时间：
1996-08-01
影响因子：
6.3
作者：
vanAsselt, DZ;vandenBroek, WJ;Hoefnagels, WH
通讯作者：
Hoefnagels, WH
影响因子：
3.2
作者：
Watanabe, Fumio;Bito, Tomohiro
通讯作者：
Bito, Tomohiro