Abstract. Keshan disease (KD) is an endemic cardiomyopathy. The etiology of KD is selenium deficiency; however, it is not the only one and there is no effective approach to preventing and curing this disease. The aim of the present study was to explore the differences in the role of arachidonic acid (AA) by the cytochrome P450 enzyme between chronic KD (CKD), dilated cardiomyopathy (DCM) and control patients. Reverse transcription-quantitative polymerase chain reaction was used to detect the CYP1A1 and CYP2C19 gene expression levels in 6 CKD patients, 6 DCM and 6 healthy controls. An enzyme-linked immunosorbent assay kit was applied to detect serum protein expression of CYP1A1 and CYP2C19, AA and epoxyeicosatrienoic acids (EETs), and 20-hydroxyeicosatetraenoic acids (20-HETE) in 67 CKD patients, 28 DCM, and 58 controls. The present results showed that the expression levels of CYP1A1 and CYP2C19 genes were significantly upregulated compared with the control group (P<0.01). The expression level of the CYP1A1 protein in the CKD (49.55±35.11 pg/ml) and DCM (46.68 ±13.01 pg/ml) groups were enhanced compared with the control group (44.33±16.76 pg/ml) (P<0.01). The production of the CYP2C19 protein in the CKD (57.52±28.22 pg/ml) and DCM (56.36±11.26 pg/ml) groups was enhanced compared with the control group (51.43±10.76 pg/ml). The concentrations of AA in the CKD (126.27±47.91 ng/ml) and DCM (133.24±58.67 ng/ml) groups were also significantly increased compared to the control (78.16±23.90 ng/ml) (P<0.001). The concentration of 20-HETE in the CKD (198.34±17.22 ng/ml) and DCM (194.46±20.35 ng/ml) groups were also significantly increased compared to the control (130.10±16.10 ng/ml) (P<0.001). The only difference between CKD and DCM was for the expression of the CYP1A1 gene and protein.The maximum concentration of EETs was in the control group (44.37±6.14 pg/ml), and the other two groups were lower than the control group (P<0.001). These findings indicated that AA-derived CYP450 metabolites may have a critical role in the pathogenesis of KD and DCM. Upregulation of the CYP2C19 gene and frequent protein expression may be a protective compensation reaction, while CYP1A1 may aggravate myocardial injury.
Abstract. XP-V is a subtype of Xeroderma pigmentosum diseases with typical pigmentation and cancers in sun-exposed regions. The present study investigated the role of in the imbalance of polymerase expression levels in XP-V tumor cells. Following software prediction results, certain miRNAs were chosen as candidate regulators for the observed imbalance in polymerases in XP-V tumor cells. Reverse transcription-quantitative polymerase chain reaction and western blot were used to test candidate miRNAs for their ability to reduce the expression of these polymerases. A luciferase reporter assay was used to further verify the western blot results. Polymerases κ and θ were expressed at lower levels in XP-V tumor cells compared to normal control cells. A positive correlation was demonstrated between miR-20b and polymerases κ and θ. It was also demonstrated that a proportion of miRNAs had no effect on polymerases κ and θ, despite the software predicting that these miRNAs would target these two polymerases. Therefore, miR-20b may be responsible for the low expression levels of polymerase κ and θ in XP-V tumor cells, which accelerated mismatch in DNA replication repairing. IntroductionXeroderma pigmentosum (XP) is a sun-toxicity disease. A total of 8 subtypes (from XP-A to XP-G and XP-V) of this disease have been identified by their different pathogenic genes (1,2). The pathogenic mechanisms of almost all these subtypes result from a defect in nucleotide excision repair (3), except XP-V subtype, which results from a translesion synthesis (TLS) defect (4). XP-V is a common subtype (21%) in XP disease, and has a similar phenotype to other subtypes (2), including sun sensitivity, photophobia, early onset of freckling, and subsequent neoplastic changes in sun-exposed skin (5,6).The majority of studies have demonstrated that XP-V disease is a result of mutations in the POLH gene (encoding DNA polymerase η). Polymerase η is the main DNA polymerase responsible for TLS, and its defect could apparently reduce TLS efficiency and increase mismatch in DNA replication. These phenomena result in genomic instability, leading to a high incidence of tumors in patients (7-15). It has been previously demonstrated that polymerase η has defective expression in XP-V cells and that certain other polymerases involving TLS are unusually expressed, such as polymerase κ and ζ (encoded by POLK and REV3 l, respectively) (16). An additional polymerase, polymerase θ (encoded by POLQ), also has low expression in XP-V cells and tumor tissue and has the same function as polymerase η, which is to generate A/T mutations during the somatic hypermutation of immunoglobulin (Ig) genes (16,17). Given that a number of polymerases change their expression in XP-V cells and tumor tissue, certain factors may co-regulate the expression of these polymerases.MicroRNAs (miRNAs) are endogenous, small non-coding RNAs that regulate translation and degradation of mRNAs at the post-transcriptional level (18). Protein expression from hundreds of genes are directly suppressed, a...
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