Abstract：
Understanding the endocannabinoid system in C. elegans may offer insights into basic biological processes and potential therapeutic targets for managing pain and inflammation in human. It is well established that anandamide modulates pain perception by binding to cannabinoid and vanilloid receptors, regulating neurotransmitter release and neuronal activity. One objective of this study was to demonstrate the suitability of C. elegans as a model organism for assessing the antinociceptive properties of bioactive compounds and learning about the role of endocannabinoid system in C. elegans. The evaluation of the compound anandamide (AEA) revealed antinociceptive activity by impeding C. elegans nocifensive response to noxious heat. Proteomic and bioinformatic investigations uncovered several pathways activated by AEA. Enrichment analysis unveiled significant involvement of ion homeostasis pathways, which are crucial for maintaining neuronal function and synaptic transmission, suggesting AEA\'s impact on neurotransmitter release and synaptic plasticity. Additionally, pathways related to translation, protein synthesis, and mTORC1 signaling were enriched, highlighting potential mechanisms underlying AEA\'s antinociceptive effects. Thermal proteome profiling identified NPR-32 and NPR-19 as primary targets of AEA, along with OCR-2, Cathepsin B, Progranulin, Transthyretin, and ribosomal proteins. These findings suggest a complex interplay between AEA and various cellular processes implicated in nociceptive pathways and inflammation modulation. Further investigation into these interactions could provide valuable insights into the therapeutic potential of AEA and its targets for the management of pain-related conditions.
摘要：
了解秀丽隐杆线虫中的内源性大麻素系统可以提供对基本生物过程和管理人类疼痛和炎症的潜在治疗目标的见解。众所周知，anandamide通过与大麻素和香草素受体结合来调节疼痛感知，调节神经递质释放和神经元活动。这项研究的一个目的是证明秀丽隐杆线虫作为模型生物的适用性，以评估生物活性化合物的抗伤害感受特性，并了解内源性大麻素系统在秀丽隐杆线虫中的作用。化合物anandamide（AEA）的评估通过阻止秀丽隐杆线虫对有害热的伤害反应来揭示抗伤害感受活性。蛋白质组学和生物信息学研究发现了AEA激活的几种途径。富集分析揭示了离子稳态途径的显著参与，这对维持神经元功能和突触传递至关重要，提示AEA对神经递质释放和突触可塑性的影响。此外,与翻译相关的途径，蛋白质合成，mTORC1信号被富集，强调AEA抗伤害作用的潜在机制。热蛋白质组分析确定NPR-32和NPR-19是AEA的主要靶标，还有OCR-2组织蛋白酶B,前颗粒蛋白,转甲状腺素,和核糖体蛋白。这些发现表明AEA和与伤害性途径和炎症调节有关的各种细胞过程之间的复杂相互作用。对这些相互作用的进一步研究可以为AEA的治疗潜力及其治疗疼痛相关疾病的目标提供有价值的见解。
