Parkinson's disease (PD) is one of the most common progressive neurodegenerative pathologies that leads to dopaminergic deficiency and motor manifestations. Alpha-synuclein aggregation is a characteristic hallmark of PD pathogenesis. These aggregates facilitate the formation of Lewy bodies and degeneration. The epidemiological evidence demonstrates a definitive association of diabetes with PD risk. Considering this, many antidiabetic agents such as GLP-1 agonists and DPP-4 inhibitors are being explored as alternative PD therapeutics. This study evaluated the neuroprotective effect of the DPP-4 inhibitor sitagliptin mediated by the PI3K/AKT and Nrf2 pathways in PD models. In silico studies were conducted to determine the binding affinity, stability, and ADMET properties of DPP-4 inhibitors with target proteins. Sitagliptin (15 mg/kg p.o.) was administered in rotenone (30 mg/kg p.o. for 28 days)-induced and MPTP/P (25 mg/kg i.p. MPTP and 100 mg/kg probenecid i.p. twice a week for 5 weeks)-induced PD mouse (C57/BL6) models. Neurobehavioral assessments were carried out throughout the study. Biochemical (GSH, MDA), molecular estimations (AKT, Nrf2, PI3K, GSK-3β, GLP1, CREB, BDNF, NF-κB, alpha-synuclein), histopathological studies, and immunohistochemistry were carried out at the end of the study. The in silico studies demonstrate better binding, stability, and ADMET profile of sitagliptin with both target proteins. Sitagliptin restored cognitive and motor deficits in both rotenone- and MPTP/P-induced mouse models. There was upregulation of PI3K, AKT, Nrf2, CREB, and BDNF levels and downregulation of GSK-3β, NF-κB, and alpha-synuclein levels in both models after treatment with sitagliptin. However, GLP1 levels were not significantly restored, indicating a GLP1-independent mechanism. It also restored histopathological alterations and TH+ neuronal loss induced by rotenone and MPTP/P. These findings demonstrate that sitagliptin exhibits neuroprotective action mediated by upregulation of the PI3K/AKT and Nrf2 pathways in rotenone and MPTP/P mouse models of PD.

• Klíčová slova
• DPP-4 inhibitors, Nrf2, PI3K/AKT, Parkinson’s disease, alpha-synuclein, sitagliptin,
• MeSH
• faktor 2 související s NF-E2 * metabolismus   účinky léků   MeSH
• fosfatidylinositol-3-kinasy * metabolismus   účinky léků   MeSH
• inhibitory dipeptidylpeptidasy 4 * farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• neuroprotektivní látky * farmakologie   MeSH
• parkinsonské poruchy metabolismus   farmakoterapie   MeSH
• protoonkogenní proteiny c-akt * metabolismus   MeSH
• rotenon MeSH
• signální transdukce účinky léků   MeSH
• sitagliptin fosfát * farmakologie   MeSH
• upregulace účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• faktor 2 související s NF-E2 * MeSH
• fosfatidylinositol-3-kinasy * MeSH
• inhibitory dipeptidylpeptidasy 4 * MeSH
• neuroprotektivní látky * MeSH
• Nfe2l2 protein, mouse MeSH Prohlížeč
• protoonkogenní proteiny c-akt * MeSH
• rotenon MeSH
• sitagliptin fosfát * MeSH

Androgen receptor-targeting agents, particularly enzalutamide, show promise in enhancing prostate cancer diagnostic and therapeutic strategies by modulating prostate-specific membrane antigen (PSMA). Methods: A retrospective clinical cohort study investigated 9 men with metastatic castration-resistant prostate cancer on enzalutamide. PSMA PET/CT scans were obtained before and after enzalutamide initiation to assess PSMA expression changes. Lesions and organs at risk were evaluated visually and semiquantitatively. The flare phenomenon was characterized by a significant increase (≥20%) in the SUVmax of existing lesions or the appearance of new PSMA-positive lesions. Results: Exposure to enzalutamide led to a significant PSMA expression increase in 56% of assessed lesions (n = 42), with new lesions detected in 1 patient (11%). PSMA expression in organs at risk remained largely unaffected, indicating a tumor-specific response. Conclusion: Enzalutamide induces PSMA upregulation in metastatic castration-resistant prostate cancer, potentially enhancing diagnostic and therapeutic strategies. Further exploration of the flare phenomenon's clinical implications is warranted.

• Klíčová slova
• ARTA, androgen receptor–targeting agent, enzalutamide, flare phenomenon, prostate cancer, prostate-specific membrane antigen,
• MeSH
• antigeny povrchové * metabolismus   MeSH
• benzamidy * MeSH
• fenylthiohydantoin * terapeutické užití   analogy a deriváty   MeSH
• glutamátkarboxypeptidasa II * metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prostaty rezistentní na kastraci * farmakoterapie   diagnostické zobrazování   metabolismus   MeSH
• nitrily * terapeutické užití   MeSH
• PET/CT * MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• upregulace * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny povrchové * MeSH
• benzamidy * MeSH
• enzalutamide MeSH Prohlížeč
• fenylthiohydantoin * MeSH
• FOLH1 protein, human MeSH Prohlížeč
• glutamátkarboxypeptidasa II * MeSH
• nitrily * MeSH

Pollen germination and pollen tube (PT) growth are extremely sensitive to high temperatures. During heat stress (HS), global translation shuts down and favors the maintenance of the essential cellular proteome for cell viability and protection against protein misfolding. Here, we demonstrate that under normal conditions, the Arabidopsis (Arabidopsis thaliana) eukaryotic translation initiation factor subunit eif3m1/eif3m2 double mutant exhibits poor pollen germination, loss of PT integrity and an increased rate of aborted seeds. Surprisingly, under HS at 37 °C, eif3m1 pollen germination outperformed wild-type Col-0, showing enhanced PT integrity. We established that the improved thermotolerance of the eif3m1 PT was due to increased expression of its putative paralog eIF3M2, which in turn upregulated Heat Shock protein 70 (HSP70) mRNA and protein levels. Indeed, eIF3M2 overexpression upregulated HSP70 expression, whereas eif3m2 knockdown showed reduced HSP70.1 promoter activity and increased in PT burst under HS conditions. Moreover, we show that eIF3M2 coimmunoprecipitates with HSP70 in PTs and directly interacts with cytoplasmic HSP70.1/2/4 and eIF4G in Nicotiana benthamiana pavement cells. Collectively, our data revealed that plants employ the eIF3M2-HSP70 module as a regulator of thermotolerance to maintain PT membrane integrity and improve fertilization and seed set adaptation under high temperatures.

• MeSH
• Arabidopsis * genetika   metabolismus   fyziologie   MeSH
• buněčná membrána metabolismus   MeSH
• eukaryotický iniciační faktor 3 metabolismus   genetika   MeSH
• klíčení genetika   MeSH
• proteiny huseníčku * metabolismus   genetika   MeSH
• proteiny tepelného šoku HSP70 * metabolismus   genetika   MeSH
• pylová láčka * růst a vývoj   genetika   metabolismus   MeSH
• reakce na tepelný šok * genetika   MeSH
• regulace genové exprese u rostlin MeSH
• upregulace genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• eukaryotický iniciační faktor 3 MeSH
• proteiny huseníčku * MeSH
• proteiny tepelného šoku HSP70 * MeSH

PURPOSE: The field cancerization concept indicates the presence of pre-cancerous changes in clinically normal tissue surrounding the tumor. In squamous cell carcinoma of the oral tongue (SCCOT) which is infrequently linked to human papillomavirus infection, we have previously reported that clinically normal tongue contralateral to tumor (NTCT) is molecularly abnormal. Here, combining our transcriptomic and genomic data, we aimed to investigate the contribution of molecular changes in NTCT to cancer development. METHODS: Microarray gene expression data of 14 healthy controls, 23 NTCT and 29 SCCOT samples were investigated to characterize transcriptional profiles in NTCT. Whole exome sequencing and RNA-sequencing data of paired NTCT and tumor samples from 15 SCCOT patients were used to study correlation between copy number variation and differential gene expression. RESULTS: Using supervised multivariate partial least squares discriminant analysis, a total of 61 mRNAs that distinguish NTCT from healthy tongue were selected. Functional enrichment analysis of the 22 upregulated genes showed increased "positive regulation of nitrogen compound metabolic process" in NTCT. All 12 genes involved in this process have roles in apoptosis (anti- and/or pro-apoptotic). Compared to healthy controls, Zinc Finger Protein 395 (ZNF395), a pro-apoptotic tumor suppressor located on chromosome 8p, was the only gene showing increased mRNA level in NTCT whereas decreased in SCCOT. Given the frequent loss of chromosome 8p in SCCOT, the impact of ZNF395 copy number variation on gene expression was further examined, revealing a positive correlation between copy number and mRNA level (correlation coefficient = 0.572, p < 0.001). CONCLUSION: NTCT is susceptible to malignant transformation, where tissue homeostasis is maintained at least partly through regulation of apoptosis. Loss of the pro-apoptotic gene ZNF395 could thus initiate cancer development.

• Klíčová slova
• ZNF395, Apoptosis, Etiologic field effect, Field cancerization, SCCOT,
• MeSH
• apoptóza * genetika   MeSH
• dlaždicobuněčné karcinomy hlavy a krku * genetika   patologie   MeSH
• dospělí MeSH
• homeostáza genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory jazyka * genetika   patologie   MeSH
• regulace genové exprese u nádorů MeSH
• senioři MeSH
• spinocelulární karcinom genetika   patologie   MeSH
• transkriptom MeSH
• upregulace * MeSH
• variabilita počtu kopií segmentů DNA MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Bordetella pertussis infects the upper airways of humans and disarms host defense by the potent immuno-subversive activities of its pertussis (PT) and adenylate cyclase (CyaA) toxins. CyaA action near-instantly ablates the bactericidal activities of sentinel CR3-expressing myeloid phagocytes by hijacking cellular signaling pathways through the unregulated production of cAMP. Moreover, CyaA-elicited cAMP signaling also inhibits the macrophage colony-stimulating factor (M-CSF)-induced differentiation of incoming inflammatory monocytes into bactericidal macrophages. We show that CyaA/cAMP signaling via protein kinase A (PKA) downregulates the M-CSF-elicited expression of monocyte receptors for transferrin (CD71) and hemoglobin-haptoglobin (CD163), as well as the expression of heme oxygenase-1 (HO-1) involved in iron liberation from internalized heme. The impact of CyaA action on CD71 and CD163 levels in differentiating monocytes is largely alleviated by the histone deacetylase inhibitor trichostatin A (TSA), indicating that CyaA/cAMP signaling triggers epigenetic silencing of genes for micronutrient acquisition receptors. These results suggest a new mechanism by which B. pertussis evades host sentinel phagocytes to achieve proliferation on airway mucosa.IMPORTANCETo establish a productive infection of the nasopharyngeal mucosa and proliferate to sufficiently high numbers that trigger rhinitis and aerosol-mediated transmission, the pertussis agent Bordetella pertussis deploys several immunosuppressive protein toxins that compromise the sentinel functions of mucosa patrolling phagocytes. We show that cAMP signaling elicited by very low concentrations (22 pM) of Bordetella adenylate cyclase toxin downregulates the iron acquisition systems of CD14+ monocytes. The resulting iron deprivation of iron, a key micronutrient, then represents an additional aspect of CyaA toxin action involved in the inhibition of differentiation of monocytes into the enlarged bactericidal macrophage cells. This corroborates the newly discovered paradigm of host defense evasion mechanisms employed by bacterial pathogens, where manipulation of cellular cAMP levels blocks monocyte to macrophage transition and replenishment of exhausted phagocytes, thereby contributing to the formation of a safe niche for pathogen proliferation and dissemination.

• Klíčová slova
• Bordetella pertussis, adenylate cyclase toxin, cyclic AMP, differentiation, iron acquisition, macrophages, monocytes,
• MeSH
• adenylátcyklasový toxin * metabolismus   genetika   MeSH
• AMP cyklický * metabolismus   MeSH
• antigen CD163 MeSH
• antigeny diferenciační myelomonocytární MeSH
• Bordetella pertussis * MeSH
• buněčná diferenciace * MeSH
• CD antigeny metabolismus   genetika   MeSH
• lidé MeSH
• lipopolysacharidové receptory * metabolismus   MeSH
• monocyty * metabolismus   imunologie   mikrobiologie   MeSH
• proteinkinasy závislé na cyklickém AMP metabolismus   MeSH
• receptory buněčného povrchu metabolismus   genetika   MeSH
• signální transdukce * MeSH
• upregulace MeSH
• železo metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenylátcyklasový toxin * MeSH
• AMP cyklický * MeSH
• antigen CD163 MeSH
• antigeny diferenciační myelomonocytární MeSH
• CD antigeny MeSH
• CD14 protein, human MeSH Prohlížeč
• lipopolysacharidové receptory * MeSH
• proteinkinasy závislé na cyklickém AMP MeSH
• receptory buněčného povrchu MeSH
• železo MeSH

AIMS: Endoplasmic reticulum stress followed by the unfolded protein response is one of the cellular mechanisms contributing to the progression of α-synuclein pathology in Parkinson's disease and other Lewy body diseases. We aimed to investigate the activation of endoplasmic reticulum stress and its correlation with α-synuclein pathology in human post-mortem brain tissue. METHODS: We analysed brain tissue from 45 subjects-14 symptomatic patients with Lewy body disease, 19 subjects with incidental Lewy body disease, and 12 healthy controls. The analysed brain regions included the medulla, pons, midbrain, striatum, amygdala and entorhinal, temporal, frontal and occipital cortex. We analysed activation of endoplasmic reticulum stress via levels of the unfolded protein response-related proteins (Grp78, eIF2α) and endoplasmic reticulum stress-regulating neurotrophic factors (MANF, CDNF). RESULTS: We showed that regional levels of two endoplasmic reticulum-localised neurotrophic factors, MANF and CDNF, did not change in response to accumulating α-synuclein pathology. The concentration of MANF negatively correlated with age in specific regions. eIF2α was upregulated in the striatum of Lewy body disease patients and correlated with increased α-synuclein levels. We found the upregulation of chaperone Grp78 in the amygdala and nigral dopaminergic neurons of Lewy body disease patients. Grp78 levels in the amygdala strongly correlated with soluble α-synuclein levels. CONCLUSIONS: Our data suggest a strong but regionally specific change in Grp78 and eIF2α levels, which positively correlates with soluble α-synuclein levels. Additionally, MANF levels decreased in dopaminergic neurons in the substantia nigra. Our research suggests that endoplasmic reticulum stress activation is not associated with Lewy pathology but rather with soluble α-synuclein concentration and disease progression.

• Klíčová slova
• ER stress, Lewy body disease, Parkinson's disease, alpha‐synuclein, unfolded protein response,
• MeSH
• alfa-synuklein * metabolismus   MeSH
• biologické markery metabolismus   MeSH
• chaperon endoplazmatického retikula BiP * metabolismus   MeSH
• demence s Lewyho tělísky * patologie   metabolismus   MeSH
• eukaryotický iniciační faktor 2 * metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mozek metabolismus   patologie   MeSH
• neurotrofní faktory metabolismus   MeSH
• proteiny teplotního šoku * metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• signální dráha UPR * fyziologie   MeSH
• stres endoplazmatického retikula fyziologie   MeSH
• upregulace * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alfa-synuklein * MeSH
• biologické markery MeSH
• chaperon endoplazmatického retikula BiP * MeSH
• EIF2S1 protein, human MeSH Prohlížeč
• eukaryotický iniciační faktor 2 * MeSH
• HSPA5 protein, human MeSH Prohlížeč
• MANF protein, human MeSH Prohlížeč
• neurotrofní faktory MeSH
• proteiny teplotního šoku * MeSH
• SNCA protein, human MeSH Prohlížeč

INTRODUCTION: IL-40 is a novel cytokine associated with autoimmune connective tissue disorders such as rheumatoid arthritis (RA) or Sjögren syndrome. We have previously shown an accumulation of IL-40 in the RA joint and its expression by immune cells and fibroblasts. Therefore, we aimed to assess the role of IL-40 in association with hyaline cartilage and chondrocyte activity. METHODS: Immunohistochemistry was employed to detect IL-40 in paired samples of loaded and unloaded regions of osteoarthritis (OA) cartilage (n=5). Synovial fluid IL-40 was analysed by ELISA in OA (n=31) and control individuals after knee injury (n=34). The impact of IL-40 on chondrocytes was tested in vitro. RESULTS: IL-40 was found in chondrocytes of the superficial zone of the OA cartilage, both in loaded and unloaded explants. Additionally, only biopsies from loaded explants showed significant IL-40 positivity in transitional zone chondrocytes. Levels of IL-40 were significantly elevated in the synovial fluid from OA patients compared to controls (p<0.0009) and correlated with synovial fluid leukocyte counts in OA (r=0.444, p=0.014). Chondrocytes exposed to IL-40 dose dependently increased in the secretion of pro-inflammatory cytokines IL-6 (p<0.0001) and IL-8 (p=0.004). Moreover, a dose dependent up-regulation of matrix degrading metalloproteinases MMP-1 (p=0.004), MMP-3 (p=0.031) and MMP-13 (p=0.0002) upon IL-40 treatment was observed in contrast to untreated chondrocytes. CONCLUSION: This study is the first to demonstrate the accumulation of IL-40 in OA cartilage and its up-regulation in the synovial fluid of OA patients compared to controls. In addition, extracellular IL-40 appears to play a role in promoting inflammation and cartilage destruction by driving chondrocyte behaviour towards a more aggressive phenotype.

• Klíčová slova
• Cartilage, Chondrocytes, Interleukin 40, Osteoarthritis,
• MeSH
• chondrocyty * metabolismus   patologie   MeSH
• dospělí MeSH
• ELISA MeSH
• fenotyp MeSH
• imunohistochemie MeSH
• interleukiny * metabolismus   MeSH
• kloubní chrupavka metabolismus   patologie   MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• osteoartróza * metabolismus   patologie   MeSH
• senioři MeSH
• synoviální tekutina * metabolismus   MeSH
• upregulace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• C17orf99 protein, human MeSH Prohlížeč
• interleukiny * MeSH

BACKGROUND/AIM: The management of patients with clear cell renal cell carcinoma (ccRCC) includes prognosis assessment based on TNM classification and biochemical markers. This approach stratifies patients with advanced ccRCC into groups of favorable, intermediate, and poor prognosis. The aim of the study was to improve prognosis estimation using microRNAs involved in the pathogenesis of ccRCC. PATIENTS AND METHODS: The study was based on a histologically-verified set of matched ccRCC FFPE tissue samples (normal renal tissue, primary tumor, metastasis, n=20+20+20). The expression of 2,549 microRNAs was analyzed using the SurePrint G3 Human miRNA microarray kit (Agilent Technologies). Prognostic value of significantly deregulated microRNAs was further evaluated on microRNA expression and clinical data of 475 patients obtained from TCGA Kidney Clear Cell Carcinoma (KIRC) database. RESULTS: There were 13 up-regulated and 6 down-regulated microRNAs in tumor tissues compared to control tissues. Among them, survival analysis revealed those with prognostic significance. Patients with high expression of miR-21, miR-27a, miR-34a, miR-106b, miR-210, and miR-342 showed significantly unfavorable outcome. The opposite was observed for miR-30e, patients with low expression had significantly shorter survival. CONCLUSION: The inclusion of these microRNAs in a prognostic panel holds the potential to enhance stratification scoring systems, on which the treatment of ccRCC patients is based.

• Klíčová slova
• Clear cell renal cell carcinoma, biomarkers, microRNA, prognosis, treatment,
• MeSH
• dospělí MeSH
• Kaplanův-Meierův odhad MeSH
• karcinom z renálních buněk * genetika   patologie   mortalita   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA * genetika   MeSH
• nádorové biomarkery * genetika   MeSH
• nádory ledvin * genetika   patologie   mortalita   metabolismus   MeSH
• prognóza MeSH
• regulace genové exprese u nádorů * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• stanovení celkové genové exprese * MeSH
• upregulace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mikro RNA * MeSH
• nádorové biomarkery * MeSH

Adhesion G protein-coupled receptors (aGPCRs) play an important role in neurodevelopment, immune defence and cancer; however, their role throughout viral infections is mostly unexplored. We have been searching for specific aGPCRs involved in SARS-CoV-2 infection of mammalian cells. In the present study, we infected human epithelial cell lines derived from lung adenocarcinoma (Calu-3) and colorectal carcinoma (Caco-2) with SARS-CoV-2 in order to analyse changes in the level of mRNA encoding individual aGPCRs at 6 and 12 h post infection. Based on significantly altered mRNA levels, we identified four aGPCR candidates-ADGRB3/BAI3, ADGRD1/GPR133, ADGRG7/GPR128 and ADGRV1/GPR98. Of these receptors, ADGRD1/GPR133 and ADGRG7/GPR128 showed the largest increase in mRNA levels in SARS-CoV-2-infected Calu-3 cells, whereas no increase was observed with heat-inactivated SARS-CoV-2 and virus-cleared conditioned media. Next, using specific siRNA, we downregulated the aGPCR candidates and analysed SARS-CoV-2 entry, replication and infectivity in both cell lines. We observed a significant decrease in the amount of SARS-CoV-2 newly released into the culture media by cells with downregulated ADGRD1/GPR133 and ADGRG7/GPR128. In addition, using a plaque assay, we observed a reduction in SARS-CoV-2 infectivity in Calu-3 cells. In summary, our data suggest that selected aGPCRs might play a role during SARS-CoV-2 infection of mammalian cells.

• Klíčová slova
• ADGRD1, ADGRG7, Caco-2, Calu-3, GPR128, GPR133, SARS-CoV-2, adhesion GPCR, mRNA expression,
• MeSH
• adenokarcinom plic * genetika   virologie   patologie   metabolismus   MeSH
• Caco-2 buňky MeSH
• COVID-19 * genetika   virologie   metabolismus   MeSH
• lidé MeSH
• messenger RNA * genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádory plic genetika   virologie   patologie   metabolismus   MeSH
• receptory spřažené s G-proteiny * metabolismus   genetika   MeSH
• SARS-CoV-2 * genetika   fyziologie   metabolismus   MeSH
• upregulace * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• messenger RNA * MeSH
• receptory spřažené s G-proteiny * MeSH

FTO and ALKBH5 proteins are essential erasers of N6-adenosine methylation in RNA. We studied how levels of FTO and ALKBH5 proteins changed during mouse embryonic development, aging, cardiomyogenesis, and neuroectodermal differentiation. We observed that aging in male and female mice was associated with FTO up-regulation in mouse hearts, brains, lungs, and kidneys, while the ALKBH5 level remained stable. FTO and ALKBH5 proteins were up-regulated during experimentally induced cardiomyogenesis, but the level of ALKBH5 protein was not changed when neuroectodermal differentiation was induced. HDAC1 depletion in mouse ES cells caused FTO down-regulation. In these cells, mRNA, carrying information from genes that regulate histone signature, RNA processing, and cell differentiation, was characterized by a reduced level of N6-adenosine methylation in specific gene loci, primarily regulating cell differentiation into neuroectoderm. Together, when we compared both RNA demethylating proteins, the FTO protein level undergoes the most significant changes during cell differentiation and aging. Thus, we conclude that during aging and neuronal differentiation, m6A RNA demethylation is likely regulated by the FTO protein but not via the function of ALKBH5.

• MeSH
• adenosin metabolismus   MeSH
• alfa-ketoglutarát-dependentní dioxygenasa, AlkB homolog 5 * genetika   metabolismus   MeSH
• buněčná diferenciace MeSH
• embryonální vývoj MeSH
• gen pro FTO * genetika   metabolismus   MeSH
• myši MeSH
• RNA metabolismus   MeSH
• stárnutí genetika   MeSH
• upregulace MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenosin MeSH
• alfa-ketoglutarát-dependentní dioxygenasa, AlkB homolog 5 * MeSH
• FTO protein, mouse MeSH Prohlížeč
• gen pro FTO * MeSH
• RNA MeSH