Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100, Burjassot, València, Spain.
Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100, Burjassot, València, Spain.
Toxicology. 2021 May 30;456:152784. doi: 10.1016/j.tox.2021.152784. Epub 2021 Apr 16.
Cell cycle progression and programmed cell death are imposed by pathological stimuli of extrinsic or intrinsic including the exposure to neurotoxins, oxidative stress and DNA damage. All can cause abrupt or delayed cell death, inactivate normal cell survival or cell death networks. Nevertheless, the mechanisms of the neuronal cell death are unresolved. One of the cell deaths triggers which have been wildly studied, correspond to mycotoxins produced by Fusarium species, which have been demonstrated cytotoxicity and neurotoxicity through impairing cell proliferation, gene expression and induction of oxidative stress. The aim of present study was to analyze the cell cycle progression and cell death pathway by flow cytometry in undifferentiated SH-SY5Y neuronal cells exposed to α-zearalenol (α-ZEL), β-zearalenol (β-ZEL) and beauvericin (BEA) over 24 h and 48 h individually and combined at the following concentration ranges: from 1.56 to 12.5 μM for α-ZEL and β-ZEL, from 0.39 to 2.5 μM for BEA, from 1.87 to 25 μM for binary combinations and from 3.43 to 27.5 μM for tertiary combination. Alterations in cell cycle were observed remarkably for β-ZEL at the highest concentration in all treatments where engaged (β-ZEL, β-ZEL + BEA and β-ZEL + α-ZEL), for both 24 h and 48 h. by activating the cell proliferation in G0/G1 phase (up to 43.6 %) and causing delays or arrests in S and G2/M phases (up to 19.6 %). Tertiary mixtures revealed increases of cell proliferation in subG0 phase by 4-folds versus control. Similarly, for cell death among individual treatments β-ZEL showed a significant growth in early apoptotic cells population at the highest concentration assayed as well as for all combination treatments where β-ZEL was involved, in both early apoptotic and apoptotic/necrotic cell death pathways.
细胞周期进程和程序性细胞死亡是由外在或内在的病理刺激引起的，包括接触神经毒素、氧化应激和 DNA 损伤。所有这些都可能导致突然或延迟的细胞死亡，使正常的细胞存活或细胞死亡网络失活。然而，神经元细胞死亡的机制尚未解决。其中一种已被广泛研究的细胞死亡触发因素是镰刀菌属产生的真菌毒素，这些毒素通过损害细胞增殖、基因表达和诱导氧化应激来表现出细胞毒性和神经毒性。本研究的目的是分析未分化的 SH-SY5Y 神经元细胞在单独和联合暴露于 α-玉米赤霉醇（α-ZEL）、β-玉米赤霉醇（β-ZEL）和 beauvericin（BEA）24 小时和 48 小时时，通过流式细胞术分析细胞周期进程和细胞死亡途径，浓度范围分别为：α-ZEL 和 β-ZEL 为 1.56 至 12.5 μM，BEA 为 0.39 至 2.5 μM，二元组合为 1.87 至 25 μM，三元组合为 3.43 至 27.5 μM。在所有处理中，β-ZEL 在最高浓度下显著改变了细胞周期，所有处理均涉及（β-ZEL、β-ZEL+BEA 和 β-ZEL+α-ZEL），无论是 24 小时还是 48 小时。通过激活 G0/G1 期的细胞增殖（高达 43.6%），并导致 S 和 G2/M 期的延迟或停滞（高达 19.6%）。三元混合物显示亚 G0 期的细胞增殖增加了 4 倍与对照相比。同样，对于单独处理的细胞死亡，β-ZEL 在最高浓度下显示早期凋亡细胞群体显著增加，以及所有涉及β-ZEL 的组合处理，在早期凋亡和凋亡/坏死细胞死亡途径中均如此。
