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食源性多环芳烃与昼夜节律紊乱

Food-Borne Polycyclic Aromatic Hydrocarbons and Circadian Disruption.

作者信息

Koh Yen-Chun, Pan Min-Hsiung

机构信息

Institute of Food Science and Technology, National Taiwan University, Taipei 106017, Taiwan.

Department of Medical Research, China Medical University Hospital, China Medical University, Taichung City 404327, Taiwan.

出版信息

ACS Omega. 2024 Jul 9;9(29):31298-31312. doi: 10.1021/acsomega.4c04120. eCollection 2024 Jul 23.

Abstract

Circadian disruption has been found to increase the risk of metabolic diseases, brain disorders, and cancer. The aryl hydrocarbon receptor (AhR), responsible for xenobiotic metabolism, is known to be activated by certain environmental stimuli, including polycyclic aromatic hydrocarbons (PAHs). Exposure to these stimuli may lead to diseases related to circadian disruption, with AhR activation suggested as a leading cause. Both the aryl hydrocarbon receptor nuclear translocator (ARNT) and aryl hydrocarbon receptor nuclear translocator-like (BMAL1) are class II basic helix-loop-helix/Per-ARNT-SIM (bHLH-PAS) proteins. These proteins form heterodimers with stimulated class I bHLH-PAS proteins, including circadian locomotor output cycles kaput (CLOCK) and AhR. Due to their sequential similarity, the overactivation of AhR by toxicants, such as PAHs, may lead to the formation of heterodimers with BMAL1, potentially causing circadian disruption. Dysregulation of BMAL1 can affect a wide range of metabolic genes, emphasizing its crucial roles. However, this issue has not been adequately addressed. Previous studies have reported that the inhibitory effects of phytochemicals on AhR activation can ameliorate diseases induced by environmental toxicants. Additionally, some phytochemicals have shown preventive effects on circadian misalignment. Therefore, this Review aims to explore potential strategies to prevent circadian disruption induced by food-borne toxicants, such as benzo[]pyrene; to generate new ideas for future studies; and to highlight the importance of investigating these preventive strategies.

摘要

昼夜节律紊乱已被发现会增加患代谢性疾病、脑部疾病和癌症的风险。芳烃受体(AhR)负责外源性物质的代谢,已知会被某些环境刺激激活,包括多环芳烃(PAHs)。接触这些刺激可能会导致与昼夜节律紊乱相关的疾病,芳烃受体激活被认为是主要原因。芳烃受体核转运蛋白(ARNT)和芳烃受体核转运蛋白样蛋白(BMAL1)均为II类碱性螺旋-环-螺旋/Per-ARNT-SIM(bHLH-PAS)蛋白。这些蛋白与受刺激的I类bHLH-PAS蛋白形成异二聚体,包括昼夜运动输出周期蛋白(CLOCK)和芳烃受体。由于它们的序列相似性,多环芳烃等毒物对芳烃受体的过度激活可能会导致与BMAL1形成异二聚体,从而可能导致昼夜节律紊乱。BMAL1的失调会影响广泛的代谢基因,凸显了其关键作用。然而,这个问题尚未得到充分解决。先前的研究报道,植物化学物质对芳烃受体激活的抑制作用可以改善环境毒物诱发的疾病。此外,一些植物化学物质对昼夜节律失调已显示出预防作用。因此,本综述旨在探索预防由食源性毒物如苯并芘引起的昼夜节律紊乱的潜在策略;为未来研究提出新思路;并强调研究这些预防策略的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c5/11270680/f052b77cd72b/ao4c04120_0001.jpg

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