At the end of the mammalian intra-uterine foetal development, a rapid switch from glycolytic to oxidative metabolism must proceed. Using microarray techniques, qPCR, enzyme activities and coenzyme Q content measurements, we describe perinatal mitochondrial metabolism acceleration in rat liver and skeletal muscle during the perinatal period and correlate the results with those in humans. Out of 1546 mitochondrial genes, we found significant changes in expression in 1119 and 827 genes in rat liver and skeletal muscle, respectively. The most remarkable expression shift occurred in the rat liver at least two days before birth. Coenzyme Q-based evaluation in both the rat model and human tissues showed the same trend: the total CoQ content is low prenatally, significantly increasing after birth in both the liver and skeletal muscle. We propose that an important regulator of rat coenzyme Q biosynthesis might be COQ8A, an atypical kinase involved in the biosynthesis of coenzyme Q. Our microarray data, a total of 16,557 RefSeq (Entrez) genes, have been deposited in NCBI's Gene Expression Omnibus and are freely available to the broad scientific community. Our microarray data could serve as a suitable background for finding key factors regulating mitochondrial metabolism and the preparation of the foetus for the transition to extra-uterine conditions.
- Klíčová slova
- coenzyme Q, human, microarray, mitochondria, prenatal, qPCR, rat, ubiquinone,
- Publikační typ
- časopisecké články MeSH
AIM: Estimating polymorphic allele frequencies of the NADPH-CYP450 oxidoreductase (POR) gene in a Czech Slavic population. METHODS: The POR gene was analyzed in 322 individuals from a control cohort by sequencing and high resolution melting analysis. RESULTS: We identified seven unreported SNP genetic variations, including two SNPs in the 5' flanking region (g.4965C>T and g.4994G>T), one intronic variant (c.1899-20C>T), one synonymous SNP (p.20Ala=) and three nonsynonymous SNPs (p.Thr29Ser, p.Pro384Leu and p.Thr529Met). The p.Pro384Leu variant exhibited reduced enzymatic activities compared with wild-type. CONCLUSION: New POR variant identification indicates the number of uncommon variants might be specific for each subpopulation being investigated, particularly germane to the singular role that POR plays in providing reducing equivalents to all CYP450s in the endoplasmic reticulum. Original submitted 15 September 2014; Revision submitted 17 November 2014.
- Klíčová slova
- CYP, Czech Slavic population, NADPH-cytochrome, P450 oxidoreductase, P450 reductase, POR, allele frequencies, haplotype, pharmacogenetics,
- MeSH
- DNA genetika MeSH
- dospělí MeSH
- frekvence genu MeSH
- genetická variace MeSH
- haplotypy MeSH
- jednonukleotidový polymorfismus * MeSH
- kinetika MeSH
- kohortové studie MeSH
- konformace proteinů MeSH
- lidé MeSH
- missense mutace MeSH
- molekulární modely MeSH
- novorozenec MeSH
- sekvence nukleotidů MeSH
- substituce aminokyselin MeSH
- systém (enzymů) cytochromů P-450 chemie genetika metabolismus MeSH
- vazebná nerovnováha MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- DNA MeSH
- POR protein, human MeSH Prohlížeč
- systém (enzymů) cytochromů P-450 MeSH
Among gynaecological cancers, epithelial ovarian cancers are the most deadly cancers while endometrial cancers are the most common diseases. Efforts to establish relevant novel diagnostic, screening and prognostic markers are aimed to help reduce the high level of mortality, chemoresistance and recurrence, particularly in ovarian cancer. MicroRNAs, the class of post-transcriptional regulators, have emerged as the promising diagnostic and prognostic markers associated with various diseased states recently. Urine has been shown as the source of microRNAs several years ago; however, there has been lack of information on urine microRNA expression in ovarian and endometrial cancers till now. In this pilot study, we examined the expression of candidate cell-free urine microRNAs in ovarian cancer and endometrial cancer patients using quantitative real-time PCR. We compared the expression between pre- and post-surgery ovarian cancer samples, and between patients with ovarian and endometrial cancers and healthy controls, within three types of experiments. These experiments evaluated three different isolation methods of urine RNA, representing two supernatant and one exosome fractions of extracellular microRNA. In ovarian cancer, we found miR-92a significantly up-regulated, and miR-106b significantly down-regulated in comparison with control samples. In endometrial cancer, only miR-106b was found down-regulated significantly compared to control samples. Using exosome RNA, no significant de-regulations in microRNAs expression could be found in either of the cancers investigated. We propose that more research should now focus on confirming the diagnostic potential of urine microRNAs in gynaecological cancers using more clinical samples and large-scale expression profiling methods.
- MeSH
- down regulace genetika MeSH
- exozómy genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA genetika moč MeSH
- nádorové biomarkery genetika moč MeSH
- nádory endometria diagnóza genetika moč MeSH
- nádory vaječníků diagnóza genetika moč MeSH
- pilotní projekty MeSH
- prognóza MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- upregulace genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- mikro RNA MeSH
- nádorové biomarkery MeSH
