Burov A V, Funikov S Yu, Astakhova T M, Teterina E V, Nebogatikov V O, Erokhov P A, Ustyugov A A, Karpov V L, Morozov A V
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
Koltsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, 119334 Russia.
Mol Biol (Mosk). 2023 Sep-Oct;57(5):886-894.
Proteasomes are key components of the ubiquitin-proteasome system. Various forms of proteasomes are known. During aging, disturbances in the functioning of proteasomes have been revealed, as well as increased expression of their particular forms. Considering these data, we studied the expression of genes encoding the constitutive and immune subunits of proteasomes in cerebral cortex samples from C57BL/6 mice at the ages of 60, 190, 380, and 720 days. In addition, the contents of constitutive and immune proteasome subunits, chymotrypsin-like and caspase-like activities of proteasome pools, as well as the activity of the β5i immune subunit were studied in tissue homogenates. The chymotrypsin-like activity and the activity of the β5i subunit of different forms of proteasomes separated by electrophoresis in native gel were characterized. Compared with samples from young animals, in the cerebral cortex of animals at an age of 720 days the following changes in the expression patterns of proteasome genes were revealed: a decreased expression of the PSMB5 gene encoding constitutive proteasome subunit β5; increased expression of genes encoding immune proteasome subunits β5i and β1i. In tissue homogenates of aged mice, an increase in the content of immune subunits β1i and β2i was shown. In samples from old animals, chymotrypsin-like activity was decreased and a tendency to a decrease in caspase-like activity of proteasomes as well as the β5i subunit activity was revealed. Analysis of the activity of native complexes in tissues obtained from old animals revealed decreased chymotrypsin-like activity of 26S and 20S proteasomes containing the β5i subunit. Based on the obtained data, it can be assumed that changes in the pool of nonconstitutive proteasomes reflect aging-associated adaptive processes in the mouse brain.
蛋白酶体是泛素-蛋白酶体系统的关键组成部分。已知有多种形式的蛋白酶体。在衰老过程中，已发现蛋白酶体功能出现紊乱，其特定形式的表达也有所增加。基于这些数据，我们研究了60、190、380和720日龄C57BL/6小鼠大脑皮质样本中编码蛋白酶体组成亚基和免疫亚基的基因表达。此外，还研究了组织匀浆中组成型和免疫蛋白酶体亚基的含量、蛋白酶体库的胰凝乳蛋白酶样和半胱天冬酶样活性，以及β5i免疫亚基的活性。对在天然凝胶中通过电泳分离的不同形式蛋白酶体的胰凝乳蛋白酶样活性和β5i亚基活性进行了表征。与幼年动物的样本相比，在720日龄动物的大脑皮质中，发现蛋白酶体基因表达模式有以下变化：编码组成型蛋白酶体亚基β5的PSMB5基因表达下降；编码免疫蛋白酶体亚基β5i和β1i的基因表达增加。在老年小鼠的组织匀浆中，免疫亚基β1i和β2i的含量有所增加。在老年动物的样本中，胰凝乳蛋白酶样活性降低，蛋白酶体的半胱天冬酶样活性以及β5i亚基活性有下降趋势。对老年动物组织中天然复合物活性的分析显示，含有β5i亚基的26S和20S蛋白酶体的胰凝乳蛋白酶样活性降低。根据所得数据，可以推测非组成型蛋白酶体库的变化反映了小鼠大脑中与衰老相关的适应性过程。
