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在BEAS-2B细胞中,尼古丁胺二烯酸诱导了能量压力和代谢重编程

Everson Willian Fialho Cordeiro¹, Elisabete Leide Marzola¹, Ricardo Soei Maekawa¹

¹Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Av. Prof. Lineu Prestes 580, CEP 05508-000 São Paulo, Brazil.

Chemical research in toxicology

|July 11, 2024

概括

低剂量的尼古丁胺 рибоoside (NR) 可能会在细胞中诱导有益的能量压力,但较高度可能是有毒的. 需要进一步的研究来探索NR的健康益处和潜在风险.

科学领域:

细胞生物学细胞生物学
代谢生物化学代谢生物化学
营养学研究营养学研究

背景情况:

尼古丁胺核糖化物 (NR) 是一种NAD+前体,研究其健康益处.
通过NR补充增加NAD+的可用性被认为是其主要的作用机制.
之前的研究强调了NR在各种实验模型中的积极影响.

研究的目的:

为了研究低剂量尼古丁胺胺 рибоoside (NR) 对人类细胞的影响.
确定NR的度依赖作用和潜在毒性.
探索NR诱导的能量压力和细胞NAD+水平之间的关系.

主要方法:

在2D单层和3D球形中培养了BEAS-2B人类细胞.
细胞暴露于不同度的NR (1-50μM).
使用枪支蛋白质组学和细胞活力测试来分析细胞反应.

主要成果:

低NR度 (1μM) 诱导了能量压力,随后在192小时后在2D培养物中增加了NAD+.
较高的NR度 (>1μM) 在2D培养物中具有细胞毒性,并在3D培养物中诱导了细胞亡.
蛋白质组学数据表明NR调节蛋白参与能量代谢,生长和生存.
预先恶化的细胞对NR细胞毒性的敏感性比正常细胞更高.

结论:

由低NR度引起的轻度能量压力可能有助于健康益处,可能通过癌症预防途径.
较高的NR度表现出细胞毒性,需要仔细考虑剂量和输送.
提高NR生物可用性的策略必须解决潜在的毒性影响.

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