PI3K-like kinases restrain Pim gene expression in endothelial cells |
| |
Authors: | Xinwen Min Jie Tang Yinfang Wang Minghua Yu Libing Zhao Handong Yang Peng Zhang Yexin Ma |
| |
Institution: | Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. minxinwen@163.com |
| |
Abstract: | Pim kinases contribute to tumor formation and development of lymphoma, which shows enhanced DNA replication, DNA recombination
and repair. Endothelial cells^(ECs) express all the three members of Pim kinase gene family. We hypothesized that DNA repair
gene would regulate Pim expression in ECs. Human umbilical vein endothelial cells (HUVECs) were isolated and maintained in
M199 culture medium. The cellular distribution of Pim-3 in ECs was determined by immunofluorescent staining. The siRNA fragments
were synthesized and transfected by using Lipofectamine LTX. The total cellular RNA was extracted from the cells by using
Trizol reagent. cDNAs were quantified by semi-quantity PCR. The effects of LY294002 and wortmannin on RNA stability in ECs
were also examined. Our data showed that LY294002 and wortmannin, phosphatidylinositol 3-kinase (PI3K) and PI3K-like kinase
inhibitors, increased Pim mRNA expression in ECs without altering the mRNA stability. RNA interference (RNAi) targeting DNA-dependent
protein kinase catalytic subunit (DNA-PKcs) and ataxia telangiectasia mutated (ATM) increased mRNA expression of Pim-3 and
Pim-1, respectively. Silencing of Akt decreased Pim-1 instead of Pm-2 and Pim-3 gene expression in ECs. But etoposide, a nucleoside
analogue, which could activate DNA-PKcs and ATM, increased Pim expression in ECs. Our study indicates that the expression
of Pim kinases is physiologically related to DNA-PKcs and ATM in ECs. |
| |
Keywords: | endothelial cell Pim-3 phosphatidylinositol 3-kinase DNA-dependent protein kinase catalytic subunit ataxia telangiectasia mutated |
本文献已被 CNKI PubMed SpringerLink 等数据库收录! |
|