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[精氨酸-血管加压素合成存在遗传性缺陷的Brattleboro大鼠植入Zajdela腹水肝癌后免疫蛋白酶体表达的特征]

[Features of the immune proteasome expression in ascite Zajdela hepatoma after implantation into Brattleboro rats with the hereditary defect of arginine-vasopressin synthesis].

作者信息

Mel'nikova V I, Khegaĭ I I, Popova N A, Lifantseva N V, Ivanova L N, Zaharova L A

出版信息

Bioorg Khim. 2014 Nov-Dec;40(6):712-9.

Abstract

The expression of the total proteasome pool, immune proteasome subunits LMP2 and LMP7, TAP1 and TAP2 transporters, as well as RT1A molecule of MHC class I was investigated in the ascite Zajdela hepatoma at the 10th day after implantation into Brattleboro rats with the hereditary defect of hypothalamic arginine-vasopressin synthesis (AVP) and into WAG rats with normal AVP expression. In Zajdela hepatoma cells implanted into Brattleboro rats the 3-fold increase of the total proteasome pool and LMP2 level and 8-fold increase of the LMP7 level was detected by Western blotting as compared to those in WAG rats. Differences in the LMP2 and LMP7 expression suggest variations in their functions, namely the important role of LMP7 in anti-tumor immunity. The growth of Zajdela hepatoma in WAG rats was accompanied by the decreased level of total proteasome pool as well as immune proteasome expression as compared to those in Brattleboro rats during the regression of tumor. The analysis of TAP1 and TAP2 revealed the pronounced expression of these peptide transporters in Zajdela hepatoma cells implanted into Brattleboro and WAG rats. The expression level of RT1A molecule of MHC class I was increased 3 times in Zajdela hepatoma cells implanted into Brattleboro rats as compared to WAG rats. Moreover, flow cytometric analysis of CD4- and CD8-lymphocytes number in the spleen of Brattleboro and WAG rats was performed at the 10th day after implantation of Zajdela hepatoma. The increased number of CD4- and CD8-lymphocytes was observed in the spleen of Brattleboro as compared to WAG. The increased subpopulations of cytotoxic T-lymphocytes and T-helpers might promote the tumor regression in Brattleboro rats. The reduced populations of CD4- and CD8-lymphocytes in the spleen of WAG rats were accompanied by the splenomegaly and tumor progression. The data obtained suggest that AVP deficiency in Brattleboro rats leads to the increase of the immune proteasome and MHC class I expression in Zajdela hepatoma cells, resulting in tumor immunogenicity and its elimination by the adaptive immunity.

摘要

在植入遗传性下丘脑精氨酸血管加压素合成缺陷(AVP)的Brattleboro大鼠和AVP表达正常的WAG大鼠10天后,研究了Zajdela肝癌腹水细胞中总蛋白酶体库、免疫蛋白酶体亚基LMP2和LMP7、TAP1和TAP2转运体以及MHC I类RT1A分子的表达。与植入WAG大鼠的Zajdela肝癌细胞相比,通过蛋白质印迹法检测到植入Brattleboro大鼠的Zajdela肝癌细胞中总蛋白酶体库和LMP2水平增加了3倍,LMP7水平增加了8倍。LMP2和LMP7表达的差异表明它们功能的变化,即LMP7在抗肿瘤免疫中的重要作用。与肿瘤消退期间的Brattleboro大鼠相比,WAG大鼠中Zajdela肝癌的生长伴随着总蛋白酶体库水平以及免疫蛋白酶体表达的降低。对TAP1和TAP2的分析显示,这些肽转运体在植入Brattleboro和WAG大鼠的Zajdela肝癌细胞中有明显表达。与WAG大鼠相比,植入Brattleboro大鼠的Zajdela肝癌细胞中MHC I类RT1A分子的表达水平增加了3倍。此外,在植入Zajdela肝癌10天后,对Brattleboro和WAG大鼠脾脏中的CD4和CD8淋巴细胞数量进行了流式细胞术分析。与WAG大鼠相比,在Brattleboro大鼠的脾脏中观察到CD4和CD8淋巴细胞数量增加。细胞毒性T淋巴细胞和T辅助细胞亚群的增加可能促进Brattleboro大鼠的肿瘤消退。WAG大鼠脾脏中CD4和CD8淋巴细胞数量的减少伴随着脾肿大和肿瘤进展。获得的数据表明,Brattleboro大鼠中的AVP缺乏导致Zajdela肝癌细胞中免疫蛋白酶体和MHC I类表达增加,从而导致肿瘤免疫原性并被适应性免疫消除。

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