Zhdanov D D, Vasina D A, Orlova V S, Orlova E V, Grishin D V, Gladilina Yu A, Pokrovskaya M V, Aleksandrova S S, Sokolov N N
Institute of Biomedical Chemistry, Moscow, Russia.
Peoples Friendship University of Russia, Moscow, Russia.
Biomed Khim. 2017 Jul;63(4):296-305. doi: 10.18097/PBMC20176304296.
Activity of telomerase catalytic subunit hTERT (human Telomerase Reverse Transcriptase) can be regulated by alternative splicing of its mRNA. At present time exact mechanism of hTERT splicing is not fully understood. Apoptotic endonuclease EndoG is known to participate this process. EndoG expression is induced by DNA damages. The aim of this work was to investigate the ability of DNA-damaging agents with different mechanism of action to induce EndoG expression and inhibit telomerase activity due to the activation of hTERT alternative splicing in normal activated human CD4+ and CD8+ T-lymphocytes. All investigated DNA-damaging agents were able to induce EndoG expression. Cisplatin, a therapeutic compound, producing DNA cross-links induced the highest level of DNA damages and EndoG expression. Incubation of CD4+ and CD8+ T-cells with cisplatin caused the changes in proportion of hTERT splice variants and inhibition of telomerase activity.
端粒酶催化亚基hTERT（人类端粒酶逆转录酶）的活性可通过其mRNA的可变剪接来调节。目前，hTERT剪接的确切机制尚未完全了解。已知凋亡核酸内切酶EndoG参与这一过程。EndoG的表达由DNA损伤诱导。这项工作的目的是研究具有不同作用机制的DNA损伤剂在正常活化的人类CD4+和CD8+ T淋巴细胞中诱导EndoG表达并通过激活hTERT可变剪接来抑制端粒酶活性的能力。所有研究的DNA损伤剂都能够诱导EndoG表达。顺铂是一种产生DNA交联的治疗化合物，可诱导最高水平的DNA损伤和EndoG表达。用顺铂孵育CD4+和CD8+ T细胞会导致hTERT剪接变体比例的变化和端粒酶活性的抑制。
