3,4-亚甲基二氧甲基苯丙胺诱导牙髓干细胞活性氧物种介导的自噬和硫氧还蛋白相互作用蛋白/核苷酸结合域、富含亮氨酸的家族、含pyrin结构域-3炎性体激活

IF 3.1 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Dental Sciences Pub Date : 2025-05-06 DOI:10.1016/j.jds.2025.04.025

Shih-Yu Lee , Shang-Wen Chiu , I-Hsun Li , Wei-Cheng Tsai , Chung-Hsing Li

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引用次数: 0

摘要

背景/目的3,4-亚甲基二氧基甲基苯丙胺（MDMA）是一种合成的取代苯丙胺。研究主要集中在其神经毒性和心理作用上，而关于其对间充质干细胞（MSCs）和牙髓干细胞（DPSCs）影响的研究相对有限。本研究探讨了MDMA对DPSCs的细胞毒性及分子机制。材料和方法采用细胞计数试剂盒、Western blot、流式细胞术和2′，7′-二氯荧光素（DCFH-DA）染料对DPSCs进行处理后，分析细胞活力、凋亡、自噬、免疫表型、活性氧（ROS）及相关信号通路。结果smdma显著降低细胞活力，增加裂解型聚腺苷二磷酸核糖聚合酶（PARP）、裂解型caspase-8、裂解型caspase-3和Bcl-2相关X蛋白（Bax），降低b细胞淋巴瘤2 （Bcl-2）。膜联蛋白V和7-氨基放线菌素D （7-AAD）流式细胞术显示这些细胞发生了早期凋亡，但未改变MSCs的免疫表型特性。MDMA还诱导ROS积累和核苷酸结合结构域、富含亮氨酸的家族、含pyrin结构域-3 （NLRP3）炎性体活化。通过腺苷活化蛋白激酶（AMPK）激活、蛋白激酶B （AKT）失活和哺乳动物雷帕霉素靶蛋白（mTOR）抑制来观察自噬激活。自噬抑制剂氯喹（CQ）可减轻mdma诱导的细胞死亡，提示过度的自噬有助于细胞损伤。结论mdma诱导ros介导的细胞自噬死亡和硫氧还蛋白相互作用蛋白(TXNIP)/NLRP3炎性体活化，造成细胞损伤。在为有MDMA使用史的患者修改牙科治疗方法时，以及在筛选DPSCs供体和接受干细胞治疗的患者时，应考虑药物成瘾的历史根源。

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3,4-methylenedioxymethamphetamine induces reactive oxygen species-mediated autophagy and thioredoxin-interactive protein/nucleotide-binding domain, leucine-rich containing family, pyrin domain-containing-3 inflammasome activation in dental pulp stem cells

Background/purpose

3,4-methylenedioxymethamphetamine (MDMA) is a synthetic substituted amphetamine. Research primarily focuses on its neurotoxicity and psychological effects, while studies examining its impact on mesenchymal stem cells (MSCs) and dental pulp stem cells (DPSCs) are relatively limited. This study investigated the cytotoxicity and molecular mechanisms of MDMA in DPSCs.

Materials and methods

Cell viability, apoptosis, autophagy, immunophenotype, reactive oxygen species (ROS), and the related signaling pathways were analyzed using a cell counting kit, Western blot, flow cytometry, and 2′,7′-dichlorofluorescein diacetate (DCFH-DA) dye after treating DPSCs with indicated concentrations of MDMA.

Results

MDMA significantly decreased cell viability and increased cleaved poly adenosine diphosphate-ribose polymerase (PARP), cleaved caspase-8, cleaved caspase-3, and Bcl-2-associated X protein (Bax), while reducing B-cell lymphoma 2 (Bcl-2). Annexin V and 7-aminoactinomycin D (7-AAD) flow cytometry showed that these cells underwent early apoptosis without altering MSCs’ immunophenotypic properties. MDMA also induced ROS accumulation and nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome activation. Autophagy activation was observed with adenosine monophosphate-activated protein kinase (AMPK) activation, protein kinase B (AKT) inactivation, and mammalian target of rapamycin (mTOR) suppression. Autophagy inhibitor chloroquine (CQ) attenuated MDMA-induced cell death, suggesting that excessive autophagy contributes to cell damage.

Conclusion

MDMA induces ROS-mediated autophagic cell death and thioredoxin-interacting protein (TXNIP)/NLRP3 inflammasome activation, causing detrimental cell damage. The historical roots of drug addiction should be considered when modifying dental approaches for patients with a history of MDMA use, as well as in the screening of DPSCs donors and patients undergoing stem cell therapy.

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来源期刊

Journal of Dental Sciences 医学-牙科与口腔外科

CiteScore

5.10

自引率

14.30%

发文量

348

审稿时长

6 days

期刊介绍： he Journal of Dental Sciences (JDS), published quarterly, is the official and open access publication of the Association for Dental Sciences of the Republic of China (ADS-ROC). The precedent journal of the JDS is the Chinese Dental Journal (CDJ) which had already been covered by MEDLINE in 1988. As the CDJ continued to prove its importance in the region, the ADS-ROC decided to move to the international community by publishing an English journal. Hence, the birth of the JDS in 2006. The JDS is indexed in the SCI Expanded since 2008. It is also indexed in Scopus, and EMCare, ScienceDirect, SIIC Data Bases. The topics covered by the JDS include all fields of basic and clinical dentistry. Some manuscripts focusing on the study of certain endemic diseases such as dental caries and periodontal diseases in particular regions of any country as well as oral pre-cancers, oral cancers, and oral submucous fibrosis related to betel nut chewing habit are also considered for publication. Besides, the JDS also publishes articles about the efficacy of a new treatment modality on oral verrucous hyperplasia or early oral squamous cell carcinoma.