González-Fernández Raquel, Grigoruţă Mariana, Chávez-Martínez Sarahi, Ruiz-May Eliel, Elizalde-Contreras José Miguel, Valero-Galván José, Martínez-Martínez Alejandro
Departamento de Ciencias Químico Biológicas, Instituto de Ciencias Biomédicas, Universidad Autónoma de Ciudad Juárez, Ciudad Juárez, Chihuahua, Mexico.
Red de Estudios Moleculares Avanzados, Instituto de Ecología A.C. (INECOL), Xalapa, Veracruz, México.
PeerJ. 2021 May 19;9:e11483. doi: 10.7717/peerj.11483. eCollection 2021.
Chronic psychological distress is considered today a pandemic due to the modern lifestyle and has been associated with various neurodegenerative, autoimmune, or systemic inflammation-related diseases. Stress is closely related to liver disease exacerbation through the high activity of the endocrine and autonomic nervous systems, and the connection between the development of these pathologies and the physiological effects induced by oxidative stress is not yet completely understood. The use of nootropics, as the cognitive enhancer and antioxidant piracetam, is attractive to repair the oxidative damage. A proteomic approach provides the possibility to obtain an in-depth comprehension of the affected cellular processes and the possible consequences for the body. Therefore, we considered to describe the effect of distress and piracetam on the liver proteome.
We used a murine model of psychological stress by predatory odor as a distress paradigm. Female Sprague-Dawley rats were distributed into four experimental groups ( = 6 - 7/group) and were exposed or not to the stressor for five days and treated or not with piracetam (600 mg/kg) for six days. We evaluated the liver proteome by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (1D-SDS-PAGE) followed by liquid chromatography-tandem mass spectrometry (GeLC-MS/MS). Besides, we analyzed the activity of liver antioxidant enzymes, the biochemical parameters in plasma and rat behavior.
Our results showed that distress altered a wide range of proteins involved in amino acids metabolism, glucose, and fatty acid mobilization and degradation on the way to produce energy, protein folding, trafficking and degradation, redox metabolism, and its implications in the development of the non-alcoholic fatty liver disease (NAFLD). Piracetam reverted the changes in metabolism caused by distress exposure, and, under physiological conditions, it increased catabolism rate directed towards energy production. These results confirm the possible relationship between chronic psychological stress and the progression of NAFLD, as well as we newly evidenced the controversial beneficial effects of piracetam. Finally, we propose new distress biomarkers in the liver as the protein DJ-1 (PARK7), glutathione peroxidase 1 (GPX), peroxiredoxin-5 (PRDX5), glutaredoxin 5 (GLRX5), and thioredoxin reductase 1 (TXNDR1), and in plasma as biochemical parameters related to kidney function such as urea and blood urea nitrogen (BUN) levels.
由于现代生活方式，慢性心理困扰如今被视为一种流行病，并且与各种神经退行性、自身免疫性或全身性炎症相关疾病有关。压力通过内分泌和自主神经系统的高活性与肝病加重密切相关，而这些病理状况的发展与氧化应激诱导的生理效应之间的联系尚未完全明了。使用促智药，如认知增强剂和抗氧化剂吡拉西坦，对于修复氧化损伤具有吸引力。蛋白质组学方法提供了深入理解受影响的细胞过程以及对身体可能产生的后果的可能性。因此，我们考虑描述心理困扰和吡拉西坦对肝脏蛋白质组的影响。
我们使用以捕食者气味作为心理应激范例的小鼠模型。将雌性斯普拉格-道利大鼠分为四个实验组（每组n = 6 - 7只），使其暴露于应激源或不暴露达五天，并给予或不给予吡拉西坦（600 mg/kg）达六天。我们通过一维十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（1D-SDS-PAGE）随后进行液相色谱-串联质谱分析（GeLC-MS/MS）来评估肝脏蛋白质组。此外，我们分析了肝脏抗氧化酶的活性、血浆中的生化参数以及大鼠行为。
我们的结果表明，心理困扰改变了广泛参与氨基酸代谢、葡萄糖和脂肪酸动员及降解以产生能量、蛋白质折叠、运输和降解、氧化还原代谢及其在非酒精性脂肪性肝病（NAFLD）发展中的作用的蛋白质。吡拉西坦逆转了由应激暴露引起的代谢变化，并且在生理条件下，它提高了指向能量产生的分解代谢率。这些结果证实了慢性心理应激与NAFLD进展之间的可能关系，并且我们新发现了吡拉西坦有争议的有益作用。最后，我们提出肝脏中的新的心理应激生物标志物为蛋白质DJ-1（PARK7）、谷胱甘肽过氧化物酶1（GPX）、过氧化物酶体增殖物激活受体5（PRDX5）、谷氧还蛋白5（GLRX5）和硫氧还蛋白还原酶1（TXNDR1），而血浆中的生物标志物为与肾功能相关的生化参数，如尿素和血尿素氮（BUN）水平。
