The Gene Expression Profile in Endothelial Cells Exposed to Mitomycin C

IF 0.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry Pub Date : 2021-08-16 DOI:10.1134/S1990750821030100

M. Yu. Sinitsky, A. V. Tsepokina, A. G. Kutikhin, D. K. Shishkova, A. V. Ponasenko

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引用次数: 3

Abstract—

The expression of genes involved in DNA repair (DDB1, ERCC4, ERCC5), leukocyte adhesion (VCAM1, ICAM1, SELE, SELP), endothelial mechanotransduction (KLF4), endothelial differentiation (PECAM1, CDH5, CD34, NOS3), endothelial-to-mesenchymal transition (SNAI1, SNAI2, TWIST1, GATA4, ZEB1, CDH2), and also coding scavenger-receptors (LOX1, SCARF1, CD36, LDLR, VLDR), antioxidant system (PXDN, CAT, SOD1) and transcription factor (HEY2) has been studied using the quantitative PCR in primary human coronary (HCAEC) and internal thoracic (HITAEC) arteries endothelial cells exposed to alkylating mutagen mitomycin C (MMC). The study was carried out two time points after 6 h of incubation with MMC and after 6 h of the genotoxic load followed by 24 h of incubation in pure culture medium. After the exposure to MMC, a decreased expression of almost all studied genes was noted in the exposed HCAEC and HITAEC; the only exception was found in the case of SNAI2, which demonstrated a 4-fold increase in its expression compared to the unexposed control. Elimination of MMC from the both cell cultures was accompanied by increased expression of the VCAM1, ICAM1, SELE, SNAI2, KLF4 genes and decreased expression of the PECAM1, CDH5, CD34, ZEB1, CAT, PXDN genes. In addition, HITAEC cells were characterized by decreased expression of the SOD1, SCARF1, CD36 genes and an increased expression of the SNAI1 and TWIST1 genes; in HCAEC, increased expression of the LDLR and VLDLR genes was noted. Thus, the genotoxic stress, induced by the alkylating mutagen MMC, is associated with the endothelial dysfunction, manifested by the altered gene expression profile of the endothelial cell cultivated under conditions of the genotoxic load.

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丝裂霉素C对内皮细胞基因表达的影响

参与DNA修复(DDB1、ERCC4、ERCC5)、白细胞粘附(VCAM1、ICAM1、SELE、SELP)、内皮机械转导(KLF4)、内皮分化(PECAM1、CDH5、CD34、NOS3)、内皮向间质转化(SNAI1、SNAI2、TWIST1、GATA4、ZEB1、CDH2)以及编码清除受体(LOX1、SCARF1、CD36、LDLR、VLDR)、抗氧化系统(PXDN、CAT、用定量PCR方法研究了烷基化诱变原丝裂霉素C (MMC)对人冠状动脉(HCAEC)和胸内动脉(HITAEC)内皮细胞中SOD1)和转录因子(HEY2)的影响。研究分别在MMC孵育6小时、基因毒性负荷6小时和纯培养基孵育24小时后两个时间点进行。暴露于MMC后，HCAEC和HITAEC中几乎所有研究基因的表达均下降;唯一的例外是SNAI2，与未暴露的对照组相比，其表达增加了4倍。MMC从两种细胞培养中消除后，VCAM1、ICAM1、SELE、SNAI2、KLF4基因的表达增加，PECAM1、CDH5、CD34、ZEB1、CAT、PXDN基因的表达降低。此外，HITAEC细胞表现为SOD1、SCARF1、CD36基因表达减少，SNAI1、TWIST1基因表达增加;在HCAEC中，LDLR和VLDLR基因的表达增加。因此，由烷基化诱变剂MMC诱导的基因毒性应激与内皮功能障碍有关，表现为在基因毒性负荷条件下培养的内皮细胞基因表达谱的改变。

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来源期刊

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry BIOCHEMISTRY & MOLECULAR BIOLOGY-

CiteScore

1.10

自引率

0.00%

发文量

期刊介绍： Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry covers all major aspects of biomedical chemistry and related areas, including proteomics and molecular biology of (patho)physiological processes, biochemistry, neurochemistry, immunochemistry and clinical chemistry, bioinformatics, gene therapy, drug design and delivery, biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine. The journal also publishes review articles. All issues of the journal usually contain solicited reviews.