A precursor of Aflatoxin B1, Versicolorin A, impairs the mitochondrial function of human intestinal Caco-2 cells

IF 10.3 1区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Environment International Pub Date : 2024-11-01 DOI:10.1016/j.envint.2024.109107

Thierry Gauthier, Sylvie Puel, Ophelie Rocher , Isabelle P. Oswald, Olivier Puel

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Abstract

Versicolorin A (VERA) is a mycotoxin produced by Aspergillus section Flavi species that is frequently detected in foodstuffs, particularly in corn. VERA is a precursor of aflatoxin B₁ (AFB₁), which is currently considered to be the most hazardous mycotoxin. While AFB₁ has been shown to impair oxidative phosphorylation (OXPHOS), the impact of VERA on mitochondrial function has not been extensively documented until now. The aim of the present study was to investigate the effect of VERA on mitochondrial function in intestinal Caco-2 cells. To this end, OXPHOS was assessed by measuring the oxygen consumption rate using the Seahorse™ real-time analyzer. In contrast to AFB₁, a low concentration of VERA (5 µM) was a strong uncoupler of OXPHOS and inhibited respiratory complexes I and III within a few minutes of exposure. After 24 h of exposure, VERA reduced the transcription of all mitochondrial genes encoding proteins involved in the electron transfer chain as well as decreasing the rate of OXPHOS. This effect was associated with the simultaneous down expression of two genes encoding proteins involved in the initiation phase of mitochondrial DNA transcription: POLRMT and TFB2M. Moreover, VERA induced down expression of genes coding for upstream key glycolytic enzymes, hexokinase and phosphofructokinase. These effects led to a reduced rate of ATP production associated with a cytotoxic effect. Given the significant implications of mitochondrial dysfunction for human health, it is crucial to consider the potential involvement of VERA in mitochondrial diseases.

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黄曲霉毒素 B1 的前体 Versicolorin A 会损害人体肠道 Caco-2 细胞的线粒体功能

黄曲霉毒素 A（VERA）是一种由黄曲霉菌（Aspergillus section Flavi）产生的霉菌毒素，经常在食品中检测到，尤其是在玉米中。VERA 是黄曲霉毒素 B1（AFB1）的前体，目前被认为是危害最大的霉菌毒素。虽然 AFB1 已被证明会损害氧化磷酸化（OXPHOS），但到目前为止，VERA 对线粒体功能的影响还没有广泛的记载。本研究旨在探讨 VERA 对肠道 Caco-2 细胞线粒体功能的影响。为此，使用 Seahorse™ 实时分析仪测量耗氧率来评估 OXPHOS。与 AFB1 不同的是，低浓度的 VERA（5 µM）是 OXPHOS 的强解偶联剂，在暴露后几分钟内就抑制了呼吸复合体 I 和 III。暴露 24 小时后，VERA 会减少编码参与电子传递链的蛋白质的所有线粒体基因的转录，并降低 OXPHOS 的速率。这种影响与两个编码参与线粒体 DNA 转录起始阶段的蛋白质的基因同时表达量减少有关：POLRMT 和 TFB2M。此外，VERA 还诱导上游关键糖酵解酶、己糖激酶和磷酸果糖激酶的编码基因表达下降。这些影响导致了与细胞毒性效应相关的 ATP 生成率降低。鉴于线粒体功能障碍对人类健康的重大影响，考虑 VERA 可能与线粒体疾病的关系至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Environment International 环境科学-环境科学

CiteScore

21.90

自引率

3.40%

发文量

734

审稿时长

2.8 months

期刊介绍： Environmental Health publishes manuscripts focusing on critical aspects of environmental and occupational medicine, including studies in toxicology and epidemiology, to illuminate the human health implications of exposure to environmental hazards. The journal adopts an open-access model and practices open peer review. It caters to scientists and practitioners across all environmental science domains, directly or indirectly impacting human health and well-being. With a commitment to enhancing the prevention of environmentally-related health risks, Environmental Health serves as a public health journal for the community and scientists engaged in matters of public health significance concerning the environment.