Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387, Cracow, Poland.
Pharmacol Rep. 2023 Apr;75(2):474-481. doi: 10.1007/s43440-023-00471-7. Epub 2023 Mar 24.
According to the World Health Organization Report, depressive disorders affect about 10% of the population. The molecular mechanism of the pathogenesis of depression is still not well understood. The new findings point to phosphatases as potential targets for effective depression therapy. The aim of the present work was the development of a method that would enable the identification of mitogen-activated protein kinase phosphatase-1 (MKP-1) protein partners using a proteomic approach.
The research was carried out using the PC12 cell line, often used as a model for neurobiological research. The use of the procedure for efficient purification of protein complexes-tandem affinity purification (TAP) will facilitate the identification of proteins interacting with MKP-1, a potential goal of effective antidepressant therapy.
Identified proteins belong to various groups: cytoskeletal, ribosomal, nucleic acid binding, chaperones, and enzymes and may potentially be involved in the molecular mechanism of depression.
The presented protocol for the purification of protein complexes is universal and can be successfully used in different mammalian cell lines. Proteins identified in the present work have been reported in the literature concerning studies on depressive disorders, which speaks in favour of their role in depression.
根据世界卫生组织的报告，抑郁障碍影响了大约 10%的人口。抑郁症发病机制的分子机制仍不完全清楚。新的发现指出磷酸酶可能是有效抗抑郁治疗的潜在靶点。本工作的目的是开发一种使用蛋白质组学方法鉴定丝裂原活化蛋白激酶磷酸酶-1（MKP-1）蛋白伴侣的方法。
本研究使用 PC12 细胞系进行，该细胞系常用于神经生物学研究的模型。使用程序进行有效的蛋白质复合物-串联亲和纯化（TAP）的纯化将有助于鉴定与 MKP-1 相互作用的蛋白质，这可能是有效抗抑郁治疗的潜在目标。
鉴定出的蛋白质属于各种组：细胞骨架、核糖体、核酸结合、伴侣和酶，可能潜在地参与抑郁症的分子机制。
本文提出的蛋白质复合物纯化方案是通用的，可以成功地用于不同的哺乳动物细胞系。本工作中鉴定的蛋白质在有关抑郁障碍的研究中已有文献报道，这表明它们在抑郁症中发挥作用。
