Orlova A Sh, Liupina Iu V, Abaturova S B, Sharova N P
Bioorg Khim. 2014 Nov-Dec;40(6):703-11. doi: 10.1134/s1068162014060119.
Formation of the central nervous system in ontogeny and function in adult mammals are controlled by universal ubiquitin-proteasome proteolytic system. The aim of this work was to study the dynamics of expression of immune proteasomes in comparison with the dynamics of ChLA and CLA proteasome and expression of the transcription factor Zif268 in the structures of the brain (cortex, hippocampus, and brainstem) in embryonic (E19, E21 days of embryonic development) and early postnatal (P1, P3, P4, P5, P7, P15 days of post-natal development) development in rats. ChLA and CLA in clarified homogenates of rat brain structures were determined by hydrolysis of fluorogenic commercial oligopeptides Suc-LLVY-AMC and Z-LLG-AMC, respectively. In the cortex and hippocampus of the brain was observed upregulation of immune subunits LMP7 during the active formation of biochemical mediatory structure and efferent neuronal projections at the period P7-P15. In the cerebral cortex during this period ChLA and CLA also are increased. In all structures of the brain the LMP2 immune subunits content was significantly increased at the period P7-P15. Contents of proteolytic constitutive subunit β1 in all structures decreased by P4 compare to P1 levels and was increased on P15 relative to the P1 levels. However, the level of expression of proteolytic constitutive subunit β5 increased in cortex, hippocampus and brainstem from E21 and reached maximum values on P3, P5 and P1, respectively with a sharp decrease to P7 in all studied structures. In all structures expression of LM P2 immune subunits and β1 constitutive subunits increased simultaneously with LMP7 immune subunits and sharply on P15. Also shown a positive correlation of increased expression regulator PA28 and constitutive β5 subunits in the hippocampus during the period P3-P5 and in the brainstem at the period P1-P5. The peculiarity of the studied brain regions during P7-P15 of rat early development is a correlation of expression of immune subunits LMP2 and LMP7 proteasome and ChLA with the expression of the transcription factor Zif268. Probably immune proteasome plays an important role in the regulation of key biochemical processes in the early ontogenesis of the central nervous system and are necessary for the emergence and realization of synaptic plasticity in the brain structures studied in rats.
个体发育过程中中枢神经系统的形成以及成年哺乳动物的功能受通用的泛素 - 蛋白酶体蛋白水解系统控制。本研究的目的是比较免疫蛋白酶体与ChLA和CLA蛋白酶体的表达动态，以及转录因子Zif268在大鼠胚胎期（胚胎发育第19、21天）和出生后早期（出生后发育第1、3、4、5、7、15天）大脑结构（皮质、海马体和脑干）中的表达动态。大鼠脑结构澄清匀浆中的ChLA和CLA分别通过荧光商业寡肽Suc - LLVY - AMC和Z - LLG - AMC的水解来测定。在出生后第7 - 15天生化介导结构和传出神经元投射的活跃形成期，在大脑的皮质和海马体中观察到免疫亚基LMP7的上调。在此期间，大脑皮质中的ChLA和CLA也增加。在出生后第7 - 15天，大脑所有结构中LMP2免疫亚基的含量显著增加。与出生后第1天相比，所有结构中蛋白水解组成亚基β1的含量在出生后第4天下降，并在出生后第15天相对于出生后第1天的水平增加。然而，蛋白水解组成亚基β5的表达水平从胚胎发育第21天起在皮质、海马体和脑干中增加，分别在出生后第3、5和1天达到最大值，之后在所有研究结构中于出生后第7天急剧下降。在所有结构中，LMP2免疫亚基和β1组成亚基的表达与LMP7免疫亚基同时增加，并在出生后第15天急剧增加。还显示在出生后第3 - 5天海马体以及出生后第1 - 5天脑干中，表达调节因子PA28和组成性β5亚基的表达增加呈正相关。大鼠早期发育出生后第7 - 15天所研究脑区的特点是蛋白酶体免疫亚基LMP2和LMP7以及ChLA的表达与转录因子Zif268的表达相关。免疫蛋白酶体可能在中枢神经系统早期个体发育过程中关键生化过程的调节中起重要作用，并且对于大鼠所研究脑结构中突触可塑性的出现和实现是必需的。
