We investigated the toxicity of benzo[a]pyrene (B[a]P), 1-nitropyrene (1-NP) and 3-nitrobenzanthrone (3-NBA) in A549 cells. Cells were treated for 4 h and 24 h with: B[a]P (0.1 and 1 μM), 1-NP (1 and 10 μM) and 3-NBA (0.5 and 5 μM). Bulky DNA adducts, lipid peroxidation, DNA and protein oxidation and mRNA expression of CYP1A1, CYP1B1, NQO1, POR, AKR1C2 and COX2 were analyzed. Bulky DNA adducts were induced after both treatment periods; the effect of 1-NP was weak. 3-NBA induced high levels of bulky DNA adducts even after 4-h treatment, suggesting rapid metabolic activation. Oxidative DNA damage was not affected. 1-NP caused protein oxidation and weak induction of lipid peroxidation after 4-h incubation. 3-NBA induced lipid peroxidation after 24-h treatment. Unlike B[a]P, induction of the aryl hydrocarbon receptor, measured as mRNA expression levels of CYP1A1 and CYP1B1, was low after treatment with polycyclic aromatic hydrocarbon (PAH) nitro-derivatives. All test compounds induced mRNA expression of NQO1, POR, and AKR1C2 after 24-h treatment. AKR1C2 expression indicates involvement of processes associated with reactive oxygen species generation. This was supported further by COX2 expression induced by 24-h treatment with 1-NP. In summary, 3-NBA was the most potent genotoxicant, whereas 1-NP exhibited the strongest oxidative properties.

• Klíčová slova
• 1-nitropyrene, 3-nitrobenzanthrone, benzo[a]pyrene, bulky DNA adducts, gene expression, oxidative damage,
• MeSH
• adukty DNA účinky léků   genetika   MeSH
• benz(a)anthraceny toxicita   MeSH
• benzopyren toxicita   MeSH
• buňky A549 MeSH
• cyklooxygenasa 2 genetika   MeSH
• cytochrom P-450 CYP1A1 genetika   MeSH
• cytochrom P450 CYP1B1 genetika   MeSH
• hydroxysteroidní dehydrogenasy genetika   MeSH
• lidé MeSH
• NAD(P)H dehydrogenasa (chinon) genetika   MeSH
• pneumocyty účinky léků   metabolismus   MeSH
• poškození DNA účinky léků   genetika   MeSH
• pyreny toxicita   MeSH
• systém (enzymů) cytochromů P-450 genetika   MeSH
• výfukové emise vozidel toxicita   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 1-nitropyrene MeSH Prohlížeč
• 3-nitrobenzanthrone MeSH Prohlížeč
• adukty DNA MeSH
• AKR1C2 protein, human MeSH Prohlížeč
• benz(a)anthraceny MeSH
• benzopyren MeSH
• cyklooxygenasa 2 MeSH
• CYP1A1 protein, human MeSH Prohlížeč
• CYP1B1 protein, human MeSH Prohlížeč
• cytochrom P-450 CYP1A1 MeSH
• cytochrom P450 CYP1B1 MeSH
• hydroxysteroidní dehydrogenasy MeSH
• NAD(P)H dehydrogenasa (chinon) MeSH
• NQO1 protein, human MeSH Prohlížeč
• POR protein, human MeSH Prohlížeč
• PTGS2 protein, human MeSH Prohlížeč
• pyreny MeSH
• systém (enzymů) cytochromů P-450 MeSH
• výfukové emise vozidel MeSH

The level of differentiation could influence sensitivity of colonic epithelial cells to various stimuli. In our study, the effects of TNF-alpha, inhibitors of arachidonic acid (AA) metabolism (baicalein, BA; indomethacin, INDO; niflumic acid, NA; nordihydroguaiaretic acid, NDGA), and/or their combinations on undifferentiated or sodium butyrate (NaBt)-differentiated human colon adenocarcinoma HT-29 cells were compared. NaBt-treated cells became growth arrested (blocked in G0/G1 phase of the cell cycle), and showed down-regulated Bcl-xL and up-regulated Bak proteins and increased expression of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX). These cells were more perceptive to anti-proliferative and apoptotic effects of TNF-alpha. Both inhibitors of LOX (BA and NDGA) and COX (INDO and NA) in higher concentrations modulated cell cycle changes accompanying NaBt-induced differentiation and induced various level of cell death in undifferentiated and differentiated cells. Most important is our finding that TNF-alpha action on proliferation and cell death can be potentiated by co-treatment of cells with AA metabolism inhibitors, and that these effects were more significant in undifferentiated cells. TNF-alpha and INDO co-treatment was associated with accumulation of cells in G0/G1 cell cycle phase, increased reactive oxygen species production, and elevated caspase-3 activity. These results indicate the role of differentiation status in the sensitivity of HT-29 cells to the anti-proliferative and proapoptotic effects of TNF-alpha, AA metabolism inhibitors, and their combinations, and imply promising possibility for novel anti-cancer strategies.

• MeSH
• adenokarcinom farmakoterapie   patologie   MeSH
• arachidonát-5-lipoxygenasa metabolismus   MeSH
• buněčná diferenciace účinky léků   MeSH
• buněčné dělení účinky léků   MeSH
• buněčný cyklus účinky léků   MeSH
• buňky HT-29 účinky léků   MeSH
• butyráty farmakologie   MeSH
• cyklooxygenasa 2 MeSH
• cyklooxygenasy metabolismus   MeSH
• flavanony * MeSH
• flavonoidy farmakologie   MeSH
• indomethacin farmakologie   MeSH
• inhibitory cyklooxygenasy 2 MeSH
• inhibitory cyklooxygenasy farmakologie   MeSH
• inhibitory lipoxygenas farmakologie   MeSH
• izoenzymy antagonisté a inhibitory   metabolismus   MeSH
• kaspasa 3 MeSH
• kaspasy účinky léků   metabolismus   MeSH
• kyselina arachidonová metabolismus   MeSH
• kyselina niflumová farmakologie   MeSH
• kyselina nordihydroguaiaretová farmakologie   MeSH
• lidé MeSH
• membránové proteiny MeSH
• nádory tračníku farmakoterapie   metabolismus   patologie   MeSH
• synergismus léků MeSH
• TNF-alfa farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• arachidonát-5-lipoxygenasa MeSH
• baicalein MeSH Prohlížeč
• butyráty MeSH
• CASP3 protein, human MeSH Prohlížeč
• cyklooxygenasa 2 MeSH
• cyklooxygenasy MeSH
• flavanony * MeSH
• flavonoidy MeSH
• indomethacin MeSH
• inhibitory cyklooxygenasy 2 MeSH
• inhibitory cyklooxygenasy MeSH
• inhibitory lipoxygenas MeSH
• izoenzymy MeSH
• kaspasa 3 MeSH
• kaspasy MeSH
• kyselina arachidonová MeSH
• kyselina niflumová MeSH
• kyselina nordihydroguaiaretová MeSH
• membránové proteiny MeSH
• PTGS2 protein, human MeSH Prohlížeč
• TNF-alfa MeSH

BACKGROUND: Breast cancer is the most common cancer in women worldwide and although mortality (129,000/year) stagnates, incidence (370,000/year) is increasing. In addition to histological type, grade, stage, hormonal and c-erbB2 status there is therefore a strong need for new and reliable prognostic and predictive factors. METHODS AND RESULTS: This minireview focuses on two potential prognostic and predictive candidates Tpl2/Cot and COX-2 and summarise information about them. CONCLUSION: Tumor progression locus 2 (Tpl2/Cot) is a serine/threonine protein kinase belonging to the family of MAP3 kinases. Activated Tpl2/Cot leads to induction of ERK1/2, JNK, NF-kappaB and p38MAPK pathways. The first study on Tpl2/Cot mRNA in breast cancer showed its increase in 40 % of cases of breast cancer but no available data exist on protein expression. Cyclo-oxygenase 2 (COX-2) is inducible by growth and inflammatory factors and contributes to the development of various tumours. Expression of COX-2 in breast cancer varied from 5-100 % in reviewed papers with significantly higher values in poorly differentiated tumours. Tpl2/Cot and COX-2 have their importance in different intracellular pathways and some of these are involved in cancer development. Briefly, the results from recent studies suggest that Tpl2/Cot and COX-2 could be prognostic factors in breast cancer.

• MeSH
• cyklooxygenasa 2 fyziologie   MeSH
• lidé MeSH
• MAP kinasy kinas (kinas) fyziologie   MeSH
• nádory prsu patofyziologie   MeSH
• protoonkogenní proteiny fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• cyklooxygenasa 2 MeSH
• MAP kinasy kinas (kinas) MeSH
• MAP3K8 protein, human MeSH Prohlížeč
• protoonkogenní proteiny MeSH
• PTGS2 protein, human MeSH Prohlížeč

OBJECTIVES: Cyclooxygenase-2 (COX-2) and tumor suppressor p53 are molecules that are linked to the oncogenesis of pancreatic cancer. COX-2 represents a key modulatory molecule in inflammation and carcinogenesis, and is known to be implicated in the positive regulation of growth and tumorigenesis. Abnormal expression of p53 is common in many human neoplasms including pancreatic cancer. Recent studies demonstrated functional interactions between p53 and COX-2. The p53-dependent upregulation of COX-2 was proposed to be another mechanism by which p53 could abate its own growth-inhibitory and apoptotic effects. METHODS: In this study, we immunohistochemically analyzed the expression of COX-2 and p53 in 95 pancreatic resection specimens [adenocarcinomas, 95 lesions; pancreatic intraepithelial neoplasias (PanINs), 155; normal ducts, 70]. RESULTS: The expression of COX-2 increased progressively with the grade of ductal lesions (P<0.00001). A statistically significant difference of COX-2 expression between normal ducts and low-grade PanINs was revealed (P=0.0042). COX-2 overexpression was demonstrated in 82 PanINs (52.9%), and in 76 adenocarcinomas (80%). No significant correlation between the grade of adenocarcinoma and COX-2 expression was revealed (P=0.2). The expression of p53 again increased progressively with the grade of lesions (P<0.00001) with a significant increase in high-grade PanINs. A correlation between COX-2 and p53 expression levels in carcinomas was revealed (P=0.0002), and an accumulation of p53 was associated with COX-2 overexpression in premalignant and malignant ductal lesions. CONCLUSION: These findings confirmed the generally accepted pancreatic cancer progression model, and supported the concept of the interactive role of COX-2 and p53 in pancreatic cancer carcinogenesis, which offers opportunities for targeted therapy and chemoprevention of pancreatic cancer using COX-2 inhibitors.

• MeSH
• adenokarcinom metabolismus   patologie   MeSH
• cyklooxygenasa 2 metabolismus   MeSH
• dospělí MeSH
• duktální karcinom pankreatu metabolismus   patologie   MeSH
• imunoenzymatické techniky MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorový supresorový protein p53 metabolismus   MeSH
• nádory slinivky břišní metabolismus   patologie   MeSH
• prekancerózy metabolismus   patologie   MeSH
• progrese nemoci MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vývody pankreatu metabolismus   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
• práce podpořená grantem MeSH
• Názvy látek
• cyklooxygenasa 2 MeSH
• nádorový supresorový protein p53 MeSH
• PTGS2 protein, human MeSH Prohlížeč

The cyclooxygenase-2 is a pro-inflammatory and cancer marker, whose mRNA stability and translation is regulated by the CUG-binding protein 2 interacting with AU-rich sequences in the 3' untranslated region. Here, we present the solution NMR structure of CUG-binding protein 2 RRM3 in complex with 5'-UUUAA-3' originating from the COX-2 3'-UTR. We show that RRM3 uses the same binding surface and protein moieties to interact with AU- and UG-rich RNA motifs, binding with low and high affinity, respectively. Using NMR spectroscopy, isothermal titration calorimetry and molecular dynamics simulations, we demonstrate that distinct sub-states characterized by different aromatic side-chain conformations at the RNA-binding surface allow for high- or low-affinity binding with functional implications. This study highlights a mechanism for RNA discrimination possibly common to multiple RRMs as several prominent members display a similar rearrangement of aromatic residues upon binding their targets.The RNA Recognition Motif (RRM) is the most ubiquitous RNA binding domain. Here the authors combined NMR and molecular dynamics simulations and show that the RRM RNA binding surface exists in different states and that a conformational switch of aromatic side-chains fine-tunes sequence specific binding affinities.

• MeSH
• 3' nepřekládaná oblast MeSH
• aminokyselinové motivy MeSH
• CELF proteiny chemie   genetika   metabolismus   MeSH
• cyklooxygenasa 2 genetika   MeSH
• fenylalanin chemie   metabolismus   MeSH
• konformace proteinů MeSH
• magnetická rezonanční spektroskopie MeSH
• messenger RNA chemie   metabolismus   MeSH
• proteiny nervové tkáně chemie   genetika   metabolismus   MeSH
• simulace molekulární dynamiky MeSH
• substituce aminokyselin MeSH
• úseky bohaté na AU MeSH
• vazebná místa MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 3' nepřekládaná oblast MeSH
• CELF proteiny MeSH
• CELF2 protein, human MeSH Prohlížeč
• cyklooxygenasa 2 MeSH
• fenylalanin MeSH
• messenger RNA MeSH
• proteiny nervové tkáně MeSH
• PTGS2 protein, human MeSH Prohlížeč

Polycyclic aromatic hydrocarbons (PAHs) may cause lipid peroxidation via reactive oxygen species generation. 15-F2t-isoprostane (IsoP), an oxidative stress marker, is formed from arachidonic acid (AA) by a free-radical induced oxidation. AA may also be converted to prostaglandins (PG) by prostaglandin-endoperoxide synthase (PTGS) induced by NF-κB. We treated human embryonic lung fibroblasts (HEL12469) with benzo[a]pyrene (B[a]P), 3-nitrobenzanthrone (3-NBA) and extractable organic matter (EOM) from ambient air particulate matter <2.5 µm for 4 and 24 h. B[a]P and 3-NBA induced expression of PAH metabolising, but not antioxidant enzymes. The concentrations of IsoP decreased, whereas the levels of AA tended to increase. Although the activity of NF-κB was not detected, the tested compounds affected the expression of prostaglandin-endoperoxide synthase 2 (PTGS2). The levels of prostaglandin E2 (PGE2) decreased following exposure to B[a]P, whereas 3-NBA exposure tended to increase PGE2 concentration. A distinct response was observed after EOM exposure: expression of PAH-metabolising enzymes was induced, IsoP levels increased after 24-h treatment but AA concentration was not affected. The activity of NF-κB increased after both exposure periods, and a significant induction of PTGS2 expression was found following 4-h treatment. Similarly to PAHs, the EOM exposure was associated with a decrease of PGE2 levels. In summary, exposure to PAHs with low pro-oxidant potential results in a decrease of IsoP levels implying 'antioxidant' properties. For such compounds, IsoP may not be a suitable marker of lipid peroxidation.

• MeSH
• aromatické hydroxylasy metabolismus   MeSH
• benz(a)anthraceny toxicita   MeSH
• benzopyren toxicita   MeSH
• cyklooxygenasa 2 metabolismus   MeSH
• dinoprost analogy a deriváty   biosyntéza   metabolismus   MeSH
• dinoproston biosyntéza   metabolismus   MeSH
• fibroblasty účinky léků   enzymologie   MeSH
• kultivované buňky MeSH
• kyselina arachidonová metabolismus   MeSH
• látky znečišťující vzduch toxicita   MeSH
• lidé MeSH
• NF-kappa B metabolismus   MeSH
• oxidační stres účinky léků   MeSH
• peroxidace lipidů účinky léků   MeSH
• pevné částice toxicita   MeSH
• plíce cytologie   účinky léků   embryologie   enzymologie   MeSH
• polycyklické aromatické uhlovodíky toxicita   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 3-nitrobenzanthrone MeSH Prohlížeč
• 8-epi-prostaglandin F2alpha MeSH Prohlížeč
• aromatické hydroxylasy MeSH
• benz(a)anthraceny MeSH
• benzopyren MeSH
• cyklooxygenasa 2 MeSH
• dinoprost MeSH
• dinoproston MeSH
• kyselina arachidonová MeSH
• látky znečišťující vzduch MeSH
• NF-kappa B MeSH
• pevné částice MeSH
• polycyklické aromatické uhlovodíky MeSH
• reaktivní formy kyslíku MeSH

The mechanism of rotator cuff injury remains to be elucidated. And COX-2 plays a dual role in skeletal muscle injury and regeneration, would be associated with the development of rotator cuff injury. Therefore, we chose human skeletal muscle cells (HSKMC) as an in vitro muscle tissue model and transfected lentivirus with overexpressed COX-2 to simulate the in vitro environment of rotator cuff injury. To investigate the specific molecular biological mechanism of COX-2, transcriptome sequencing (RNA-Seq) was used to analyze the differentially expressed mRNAs in HSKMC overexpressing COX-2. Enrichment analysis was performed to analyze these differentially expressed genes and real-time quantitative PCR (RT-qPCR) was used to examine the mRNA levels of genes induced by overexpression. Subsequently, the role of COX-2 in cell proliferation was confirmed by cell counting kit-8 (CCK-8), and focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) phosphorylation induced by COX-2 was utilized by western blotting (WB). The results showed that total of 30,759 differentially expressed genes were obtained, and the expression of CYP4F3 and GPR87 was significantly increased. COX-2 could bind CYP4F3 and GPR87 and co-localize with them in the cytoplasm. Finally, COX-2 promoted the proliferation of human skeletal muscle cells by activating the FAK and STAT3 pathways.

• MeSH
• cyklooxygenasa 2 * metabolismus   genetika   MeSH
• kosterní svalová vlákna metabolismus   enzymologie   patologie   MeSH
• kosterní svaly metabolismus   patologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• poranění rotátorové manžety * metabolismus   patologie   enzymologie   genetika   MeSH
• proliferace buněk MeSH
• transkripční faktor STAT3 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cyklooxygenasa 2 * MeSH
• PTGS2 protein, human MeSH Prohlížeč
• STAT3 protein, human MeSH Prohlížeč
• transkripční faktor STAT3 MeSH

AIM: To evaluate the expression of epithelial markers of colorectal carcinogenesis in patients with long-term ulcerative colitis (UC) and primary sclerosing cholangitis (PSC) before and after transplantation. METHODS: Eight patients with UC and PSC prior to liver transplantation (PSC-UC), 22 patients with UC after liver transplantation for PSC (OLT), 9 patients with active ulcerative colitis without PSC (UCA), 7 patients with UC in remission (UCR) and 10 controls (N) underwent colonoscopy with multiple biopsies. Specimens were analysed histologically and semi-quantitatively immunohistochemically for p53, Bcl-2 and cyclooxygenase-2 (COX-2) markers. Statistical analysis was performed by Kruskal-Wallis and Fisher's exact tests. RESULTS: PSC-UC had a statistically significantly higher expression of p53 in the nondysplastic mucosa as compared to OLT, UCA, UCR and N (P < 0.05). We also found a statistically significant positive correlation between the incidence of PSC and the expression of p53 (P < 0.001). UCA had a higher p53 expression as compared to UCR. OLT had a significantly lower expression of p53 as compared with PSC-UC (P < 0.001). Bcl-2 had a significant higher bcl-2 expression as compared with controls. No difference in COX-2 expression between PSC-UC, UCR and UCA was found. UCA had higher COX-2 expression as compared to UCR. We also found a statistically significant positive correlation between the expression of COX-2 and p53. Patients after liver transplantation for PSC had a statistically significantly lower expression of the p53 compared with PSC-UC (P < 0.001). PSC-UC had the same inflammatory endoscopic activity as OLT and UCR when evaluated with the Mayo score. CONCLUSION: Our study shows that the nondysplatic mucosa of UC patients with PSC is characterised by a higher expression of the tumour suppressor gene p53, suggesting a higher susceptibility of cancer. This p53 overexpression correlates with the presence of PSC whilst it is not present in patients with UC after liver transplantation for PSC.

• Klíčová slova
• Colorectal carcinoma, Cyclooxygenase-2, Imunohistochemistry, Liver transplantation, Primary sclerosing cholangitis, Ulcerative colitis, bcl2, p53,
• MeSH
• biopsie MeSH
• cyklooxygenasa 2 analýza   MeSH
• dospělí MeSH
• imunohistochemie MeSH
• kolonoskopie MeSH
• kolorektální nádory chemie   etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery analýza   MeSH
• nádorový supresorový protein p53 analýza   MeSH
• protoonkogenní proteiny c-bcl-2 analýza   MeSH
• senioři MeSH
• sklerozující cholangitida etiologie   metabolismus   chirurgie   MeSH
• studie případů a kontrol MeSH
• transplantace jater MeSH
• ulcerózní kolitida komplikace   metabolismus   chirurgie   MeSH
• upregulace MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cyklooxygenasa 2 MeSH
• nádorové biomarkery MeSH
• nádorový supresorový protein p53 MeSH
• protoonkogenní proteiny c-bcl-2 MeSH
• PTGS2 protein, human MeSH Prohlížeč
• TP53 protein, human MeSH Prohlížeč

BACKGROUND: Inflammatory bowel diseases including long-standing ulcerative colitis (UC) have an increased risk of evolving into colorectal cancer (CRC). The overexpression of some proproliferative and antiapoptotic genes, such as survivin, telomerase catalytic subunit (hTERT), integrin-linked kinase (ILK), and regulatory factors c-MYB and Tcf-4, has been implicated in the development and progression of several human malignancies including CRC. METHODS: In this study we analyzed the expression alterations of these markers and proinflammatory enzymes cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) during the transition of colonic mucosa from chronic inflammation to epithelial neoplasia in biopsies of UC patients using quantitative real-time polymerase chain reaction and immunohistochemistry; additionally, we compared the expression profiles of this gene panel in samples of patients with CRC after tumor resection and in human tumor xenografts of SW620 malignant colonic cells. RESULTS: The transcript levels of survivin, c-MYB, COX-2, iNOS, and Tcf-4 showed a statistically significant increase during neoplastic transformation of UC patient colonic mucosa, whereas hTERT and ILK were not elevated. In contrast, the specimens of CRC showed upregulated expression of not only survivin, c-MYB, Tcf-4, COX-2, and iNOS but also hTERT. A similar expression profile was observed in human tumor xenografts in which all transcripts with the exception of c-MYB were upregulated. CONCLUSIONS: These results suggest that telomerase and ILK activation occurs during the later stages of carcinoma progression, whereas upregulation of survivin, c-MYB, and Tcf-4 is a feature of the early stage of development of neoplasia, and thus, they might serve as early indicators for UC-associated colorectal carcinogenesis.

• MeSH
• apoptóza MeSH
• cyklooxygenasa 2 genetika   metabolismus   MeSH
• dospělí MeSH
• geny myb genetika   MeSH
• imunoenzymatické techniky MeSH
• inhibitory apoptózy MeSH
• kolorektální nádory etiologie   metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• myši nahé MeSH
• myši MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• prognóza MeSH
• proliferace buněk MeSH
• proteiny asociované s mikrotubuly genetika   metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• survivin MeSH
• synthasa oxidu dusnatého, typ II genetika   metabolismus   MeSH
• telomerasa genetika   metabolismus   MeSH
• transkripční faktor 4 MeSH
• transkripční faktory BHLH-Zip genetika   metabolismus   MeSH
• transkripční faktory genetika   metabolismus   MeSH
• ulcerózní kolitida komplikace   genetika   metabolismus   MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• BIRC5 protein, human MeSH Prohlížeč
• cyklooxygenasa 2 MeSH
• inhibitory apoptózy MeSH
• messenger RNA MeSH
• NOS2 protein, human MeSH Prohlížeč
• proteiny asociované s mikrotubuly MeSH
• PTGS2 protein, human MeSH Prohlížeč
• survivin MeSH
• synthasa oxidu dusnatého, typ II MeSH
• TCF4 protein, human MeSH Prohlížeč
• telomerasa MeSH
• TERT protein, human MeSH Prohlížeč
• transkripční faktor 4 MeSH
• transkripční faktory BHLH-Zip MeSH
• transkripční faktory MeSH

The human intracellular enzyme AKR1B1 belongs to the aldo-keto reductase superfamily. The AKR1B1-catalyzed reduction of aldehydes is part of the intracellular inflammatory pathway leading to the activation of NF-κB and the expression of pro-inflammatory genes. The present study is aimed at determining the inhibition of AKR1B1 brought about by an extract of artichoke leaves (bracts), and the effects of this extract and three participating compounds on the expression of AKR1B1, COX-2, and MMP-2 proteins in THP-1 cells. It seeks to identify the ability of the test substances to modulate the lipopolysaccharide (LPS)-induced activation of NF-κB in cells and the intracellular oxidant effect of test substances after incubation with LPS. Low concentrations of the extract inhibit the enzyme AKR1B1. After stimulation by LPS, the extract attenuated the activity of NF-κB in THP-1 cells, but no changes in the expression of AKR1B1 were recorded. The extract diminished the expression of the inflammation-related enzymes COX-2 and MMP-2, probably by inhibiting the activity of NF-κB. The extract significantly diminished the intracellular reactive oxygen species after a brief LPS incubation, which may also have reduced intracellular inflammation. The diminished activity of NF-κB in the cells could be linked to the inhibition of the activity of AKR1B1. Copyright © 2017 John Wiley & Sons, Ltd.

• Klíčová slova
• Cynara cardunculus, aldose reductase, antioxidant, inflammation,
• MeSH
• aldehydreduktasa antagonisté a inhibitory   genetika   metabolismus   MeSH
• cyklooxygenasa 2 metabolismus   MeSH
• Cynara scolymus chemie   MeSH
• down regulace účinky léků   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• leukemie genetika   metabolismus   patologie   MeSH
• lidé MeSH
• lipopolysacharidy MeSH
• listy rostlin chemie   MeSH
• matrixová metaloproteinasa 2 genetika   metabolismus   MeSH
• regulace genové exprese účinky léků   MeSH
• rostlinné extrakty farmakologie   MeSH
• signální transdukce účinky léků   genetika   MeSH
• transkripční faktor RelA antagonisté a inhibitory   metabolismus   MeSH
• zánět chemicky indukované   genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• AKR1B1 protein, human MeSH Prohlížeč
• aldehydreduktasa MeSH
• cyklooxygenasa 2 MeSH
• lipopolysacharidy MeSH
• matrixová metaloproteinasa 2 MeSH
• RELA protein, human MeSH Prohlížeč
• rostlinné extrakty MeSH
• transkripční faktor RelA MeSH