Skóra Bartosz, Piechowiak Tomasz, Szychowski Konrad A
Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management in Rzeszow, St. Sucharskiego 2, 35-225, Rzeszów, Poland.
Department of Chemistry and Food Toxicology, Institute of Food Technology and Nutrition, University of Rzeszow, St. Ćwiklinskiej 2, 35-601, Rzeszów, Poland.
Mol Neurobiol. 2025 Jan;62(1):819-831. doi: 10.1007/s12035-024-04298-y. Epub 2024 Jun 24.
Elastin is a stable protein present in many tissues, including brain tissues, and is one of the most long-life proteins with a half-life of approximately 70 years. The peptide with a Val-Gly-Val-Ala-Pro-Gly (VGVAPG) amino acid sequence is released during elastin decay, which correlates with aging-related neurodegeneration. A recent study has shown enhanced protein expression of Sirtuin 2 (SIRT2 - one of the redox homeostatic factors) in aged rodent brains, while the correlation between VGVAPG and SIRT2 has never been evaluated so far. Therefore, the study aimed to determine the impact of the VGVAPG hexapeptide on SIRT2 and neuronal functions in differentiated SH-SY5Y cells at the gene and protein expression levels. The present results showed that VGVAPG caused a 52.69% decrease in the level of reactive oxygen species (ROS), as in the case of neurons treated with AGK2 (Sirtuin 2 inhibitor) after 24h and 48h. Furthermore, a decrease in superoxide dismutase (SOD) activity was observed. The SIRT2 gene expression was found to fluctuate after 6h and 24h as a result of the exposure to the VGVAPG peptide. In turn, a decrease in the PPARγ, P53, SOD2, and CAT mRNA expression was shown in VGVAPG-treated cells. Additionally, an increase in the Sirtuin 2 protein expression was recorded after 24h and 48h in the VGVAPG peptide-treated neurons. Last but not least, the decrease in the level of acetylation of α-tubulin after the hexapeptide treatment was correlated with shortening of neurites, which may indicate the destabilization of the microtubule and ROS-independent induction of neurodegeneration.
弹性蛋白是一种存在于包括脑组织在内的许多组织中的稳定蛋白质，是寿命最长的蛋白质之一，半衰期约为70年。具有Val-Gly-Val-Ala-Pro-Gly（VGVAPG）氨基酸序列的肽在弹性蛋白降解过程中释放，这与衰老相关的神经退行性变有关。最近的一项研究表明，老年啮齿动物大脑中沉默调节蛋白2（SIRT2，一种氧化还原稳态因子）的蛋白质表达增强，而VGVAPG与SIRT2之间的相关性迄今为止从未被评估过。因此，该研究旨在确定VGVAPG六肽在基因和蛋白质表达水平上对分化的SH-SY5Y细胞中SIRT2和神经元功能的影响。目前的结果表明，VGVAPG使活性氧（ROS）水平降低了52.69%，这与用AGK2（沉默调节蛋白2抑制剂）处理24小时和48小时后的神经元情况相同。此外，观察到超氧化物歧化酶（SOD）活性降低。由于暴露于VGVAPG肽，发现SIRT2基因表达在6小时和24小时后波动。反过来，在VGVAPG处理的细胞中，PPARγ、P53、SOD2和CAT mRNA表达降低。此外，在VGVAPG肽处理的神经元中，24小时和48小时后沉默调节蛋白2的蛋白质表达增加。最后但同样重要的是，六肽处理后α-微管蛋白乙酰化水平的降低与神经突缩短相关，这可能表明微管的不稳定和ROS非依赖性神经退行性变的诱导。
