Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225, Rzeszow, Poland.
Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225, Rzeszow, Poland.
Neurochem Int. 2022 Oct;159:105405. doi: 10.1016/j.neuint.2022.105405. Epub 2022 Aug 5.
Elastin-derived peptides (EDPs) contain replications of the Val-Gly-Val-Ala-Pro-Gly (VGVAPG) hexapeptide. It has been described that the VGVAPG peptide induces reactive oxygen species (ROS) production in murine monocytes and astrocytes, human fibroblasts, and the human neuroblastoma (SH-SY5Y) cell line. To date, there is growing evidence that calcium channel blockers (CCBs) reduce oxidative stress and development of inflammation in the nervous system. Therefore, the aim of the present study was to evaluate the impact of such CCBs as Nifedipine, Verapamil, and MK-801 on the expression of peroxisome proliferator-activated receptor (Pparγ), i.e. ROS-related and inflammation-related proteins, in mouse astrocytes exposed in vitro to the VGVAPG peptide. The experiments showed that Nifedipine or MK-801 used in co-treatment with the VGVAPG peptide potentiated the effect of this peptide on the Pparγ level after the 24-h and 48-h treatment. Moreover, all studied compounds decreased the VGVAPG-induced caspase-1 activity in both time intervals. The data also showed that the VGVAPG peptide decreased the interleukin 1 beta (IL-1β) level in both studied time intervals. Upon a short-time exposure, the use of CCBs intensified the decrease in IL-1β stimulated by the VGVAPG peptide, opposite to the longer treatment. Moreover, the VGVAPG peptide decreased the IL-1βR1 level in both studied time intervals. After 24 h, Nifedipine and Verapamil potentiated the effect of the VGVAPG peptide. The VGVAPG peptide decreased the catalase (Cat) protein expression only after 24 h, whereas CCBs did not affect the expression of Cat induced by the VGVAPG peptide. The VGVAPG peptide increased the expression of the superoxide dismutase 1 (Sod1) protein. After 24 h of exposure, Nifedipine and Verapamil potentiated the increase in the Sod1 protein expression. Finally, our data showed that VGVAPG did not change the level of estradiol (E) in the astrocytes. Interestingly, Nifedipine and Verapamil in co-treatment with VGVAPG increased the E level. Summarizing, it can be assumed that increased amounts of the VGVAPG during lifetime can play a certain role in calcium channel functioning in neurodegenerative diseases.
弹性蛋白衍生肽（EDPs）含有 Val-Gly-Val-Ala-Pro-Gly（VGVAPG）六肽的重复序列。已经描述了 VGVAPG 肽在鼠单核细胞和星形胶质细胞、人成纤维细胞和人神经母细胞瘤（SH-SY5Y）细胞系中诱导活性氧物种（ROS）的产生。迄今为止，越来越多的证据表明钙通道阻滞剂（CCBs）可减少神经系统中的氧化应激和炎症的发展。因此，本研究的目的是评估硝苯地平、维拉帕米和 MK-801 等 CCB 对体外暴露于 VGVAPG 肽的小鼠星形胶质细胞中过氧化物酶体增殖物激活受体（Pparγ）即 ROS 相关和炎症相关蛋白表达的影响。实验表明，硝苯地平或 MK-801 与 VGVAPG 肽共同处理可增强该肽在 24 小时和 48 小时处理后对 Pparγ 水平的作用。此外，所有研究的化合物均降低了 VGVAPG 诱导的 caspase-1 活性在两个时间间隔内。数据还表明，VGVAPG 肽在两个研究时间间隔内降低了白细胞介素 1β（IL-1β）的水平。在短时间暴露下，CCBs 的使用加剧了 VGVAPG 肽刺激的 IL-1β 的减少，与较长的治疗相反。此外，VGVAPG 肽降低了两个研究时间间隔内的 IL-1βR1 水平。24 小时后，硝苯地平与维拉帕米增强了 VGVAPG 肽的作用。VGVAPG 肽仅在 24 小时后降低了过氧化氢酶（Cat）蛋白的表达，而 CCB 并未影响 VGVAPG 肽诱导的 Cat 表达。VGVAPG 肽增加了超氧化物歧化酶 1（Sod1）蛋白的表达。暴露 24 小时后，硝苯地平与维拉帕米增强了 Sod1 蛋白表达的增加。最后，我们的数据表明，VGVAPG 肽并未改变星形胶质细胞中的雌二醇（E）水平。有趣的是，硝苯地平与维拉帕米在与 VGVAPG 肽共同处理时增加了 E 水平。综上所述，可以假设一生中 VGVAPG 含量的增加可能在神经退行性疾病中的钙通道功能中发挥一定作用。
