Toxicology and Diseases Group, Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Department of Biotechnology, University of Tehran, Tehran, Iran.
Life Sci. 2020 Sep 1;256:117969. doi: 10.1016/j.lfs.2020.117969. Epub 2020 Jun 15.
Cannabinoids are the chemical compounds with a high affinity for cannabinoid receptors affecting the central nervous system through the release of neurotransmitters. However, the current knowledge related to the role of such compounds in the regulation of cellular aging is limited. This study aimed to investigate the effect of cannabidiol and tetrahydrocannabinol on the function of aged pancreatic islets.
The expression of p53, p38, p21, p16, and Glut2 genes and β-galactosidase activity were measured as hallmarks of cell aging applying real-time PCR, ELISA, and immunocytochemistry techniques. Pdx1 protein expression, insulin release, and oxidative stress markers were compared between young and aged rat pancreatic islet cells.
Upon the treatment of aged pancreatic islets cells with cannabidiol and tetrahydrocannabinol, the expression of p53, p38, p21 and the activity of β-galactosidase were reduced. Cannabidiol and tetrahydrocannabinol increase insulin release, Pdx1, Glut2, and thiol molecules expression, while the oxidative stress parameters were decreased. The enhanced expression of Pdx1 and insulin release in aged pancreatic islet cells reflects the extension of cell healthy aging due to the significant reduction of ROS.
This study provides evidence for the involvement of cannabidiol and tetrahydrocannabinol in the oxidation process of cellular aging.
大麻素是与大麻素受体具有高亲和力的化合物,通过神经递质的释放影响中枢神经系统。然而,目前关于此类化合物在细胞衰老调控中的作用的知识有限。本研究旨在探讨大麻二酚和四氢大麻酚对衰老胰岛功能的影响。
应用实时 PCR、ELISA 和免疫细胞化学技术,测量 p53、p38、p21、p16 和 Glut2 基因的表达以及β-半乳糖苷酶活性,作为细胞衰老的标志物。比较年轻和衰老大鼠胰岛细胞中 Pdx1 蛋白表达、胰岛素释放和氧化应激标志物。
用大麻二酚和四氢大麻酚处理衰老的胰岛细胞后,p53、p38、p21 的表达和β-半乳糖苷酶的活性降低。大麻二酚和四氢大麻酚增加胰岛素释放、Pdx1、Glut2 和巯基分子的表达,同时降低氧化应激参数。衰老胰岛细胞中 Pdx1 和胰岛素释放的增强表达反映了由于 ROS 显著减少,细胞健康衰老的延长。
本研究为大麻二酚和四氢大麻酚参与细胞衰老的氧化过程提供了证据。