Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine that can trigger apoptosis in many types of human cancer cells via engagement of its two pro-apoptotic receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). TRAIL can also activate several other signaling pathways such as activation of stress kinases, canonical NF-κB signaling and necroptosis. Though both receptors are ubiquitously expressed, their relative participation in TRAIL-induced signaling is still largely unknown. To analyze TRAIL receptor-specific signaling, we prepared Strep-tagged, trimerized variants of recombinant human TRAIL with high affinity for either DR4 or DR5 receptor. Using these receptor-specific ligands, we examined the contribution of individual pro-apoptotic receptors to TRAIL-induced signaling pathways. We found that in TRAIL-resistant colorectal HT-29 cells but not in pancreatic PANC-1 cancer cells, DISC formation and initial caspase-8 processing proceeds comparably via both DR4- and DR5-activated signaling. TRAIL-induced apoptosis, enhanced by the inhibitor of the Bcl-2 family ABT-737, or by the translation inhibitor homoharringtonine, proceeded in both cell lines predominantly via the DR5 receptor. ShRNA-mediated downregulation of DR4 or DR5 receptors in HT-29 cells also pointed to a stronger contribution of DR5 in TRAIL-induced apoptosis. In contrast to apoptosis, necroptotic signaling was activated similarly by both DR4- or DR5-specific ligands. Activation of auxiliary signaling pathways involving NF-κB or stress kinases proceeded under apoptotic conditions mainly in a DR5-dependent manner, while these signaling pathways were during necroptosis similarly activated by either of these ligands. Our study provides the first systematic insight into DR4-/DR5-specific signaling in colorectal and pancreatic cancer cells.

• MeSH
• apoptóza genetika   MeSH
• buňky HT-29 MeSH
• kaspasa 8 genetika   MeSH
• kolorektální nádory genetika   patologie   MeSH
• lidé MeSH
• malá interferující RNA MeSH
• nádory slinivky břišní genetika   patologie   MeSH
• nekróza genetika   patologie   MeSH
• NF-kappa B genetika   MeSH
• pankreas metabolismus   patologie   MeSH
• proliferace buněk genetika   MeSH
• protein TRAIL genetika   MeSH
• regulace genové exprese u nádorů MeSH
• signální transdukce genetika   MeSH
• TRAIL receptory genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In this review, we discuss the origin, possible biological meaning, quantitative and qualitative changes in the concentrations of cell-free nucleic acids in human circulation with regard to renal failure and the process of dialysis. We focus on the inflammatory response and apoptosis known to be in close relationship not only with hemodialysis but also with different comorbidities frequently detected in hemodialyzed patients. 
Hemodialysis itself is able to promote the changes in the quantity and quality of circulating nucleic acid pool, but large spectrum of comorbidities in hemodialyzed subjects can further complicate the interpretations of results of cell-free nucleic acid analysis. Such analysis can provide additional information about the patient prognosis and monitor some aspects of comorbidity development. Recently, it has been shown that the analysis of cell-free nucleic acids may also be worthy in patients on peritoneal dialysis because the cell-free nucleic acids may also be detected in overnight effluents and their examination can be informative with regard to the functional state of the patient's peritoneum. 
We summarize what is recently known about the use of cell-free nucleic acids as biomarkers in patients with renal failure not only in hemodialysis but also in peritoneal dialysis and we describe the future perspectives in this field.

• MeSH
• apoptóza genetika   MeSH
• biologické markery krev   MeSH
• chronické selhání ledvin krev   terapie   MeSH
• dialýza ledvin * MeSH
• DNA krev   MeSH
• komorbidita MeSH
• lidé MeSH
• messenger RNA krev   MeSH
• mikro RNA krev   MeSH
• nekróza genetika   MeSH
• nukleové kyseliny krev   MeSH
• peritoneální dialýza MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND AND AIMS: Cytokinins are positive regulators of shoot development. However, it has previously been demonstrated that efficient activation of the cytokinin biosynthesis gene ipt can cause necrotic lesions and wilting in tobacco leaves. Some plant pathogens reportedly use their ability to produce cytokinins in disease development. In response to pathogen attacks, plants can trigger a hypersensitive response that rapidly kills cells near the infection site, depriving the pathogen of nutrients and preventing its spread. In this study, a diverse set of processes that link ipt activation to necrotic lesion formation were investigated in order to evaluate the potential of cytokinins as signals and/or mediators in plant defence against pathogens. METHODS: The binary pOp-ipt/LhGR system for dexamethasone-inducible ipt expression was used to increase endogenous cytokinin levels in transgenic tobacco. Changes in the levels of cytokinins and the stress hormones salicylic, jasmonic and abscisic acid following ipt activation were determined by ultra-performance liquid chromatography-electrospray tandem mass spectrometry (UPLC-MS/MS). Trends in hydrogen peroxide content and lipid peroxidation were monitored using the potassium iodide and malondialdehyde assays. The subcellular distribution of hydrogen peroxide was investigated using 3,3'-diaminobenzidine staining. The dynamics of transcripts related to photosynthesis and pathogen response were analysed by reverse transcription followed by quantitative PCR. The effects of cytokinins on photosynthesis were deciphered by analysing changes in chlorophyll fluorescence and leaf gas exchange. KEY RESULTS: Plants can produce sufficiently high levels of cytokinins to trigger fast cell death without any intervening chlorosis - a hallmark of the hypersensitive response. The results suggest that chloroplastic hydrogen peroxide orchestrates the molecular responses underpinning the hypersensitive-like response, including the inhibition of photosynthesis, elevated levels of stress hormones, oxidative membrane damage and stomatal closure. CONCLUSIONS: Necrotic lesion formation triggered by ipt activation closely resembles the hypersensitive response. Cytokinins may thus act as signals and/or mediators in plant defence against pathogen attack.

• MeSH
• alkyltransferasy a aryltransferasy genetika   MeSH
• buněčná smrt MeSH
• chlorofyl metabolismus   MeSH
• chloroplasty genetika   metabolismus   MeSH
• cytokininy genetika   metabolismus   MeSH
• dexamethason farmakologie   MeSH
• fotosyntéza genetika   MeSH
• geneticky modifikované rostliny MeSH
• interakce hostitele a patogenu * MeSH
• listy rostlin cytologie   genetika   fyziologie   MeSH
• nekróza genetika   MeSH
• oxidační stres genetika   MeSH
• peroxid vodíku metabolismus   MeSH
• peroxidace lipidů MeSH
• průduchy rostlin fyziologie   MeSH
• regulace genové exprese u rostlin účinky léků   MeSH
• regulátory růstu rostlin genetika   metabolismus   MeSH
• tabák genetika   mikrobiologie   fyziologie   MeSH
• umlčování genů MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

MicroRNAs are emerging as important regulators of cardiac function. This study investigated the role of microRNA-24 (miR-24) in ischemic cardiomyocytes, based on the observation that miR-24 expression was significantly enhanced in the ischemic myocardium of rats. Using primary cultured rat cardiomyocytes, cell injury was induced by ischemic conditions, and the cells were evaluated for changes in lactate dehydrogenase (LDH) release, cell viability, apoptosis and necrosis. The results showed that miR-24 was increased in myocytes exposed to ischemia. When miR-24 was further overexpressed in ischemic myocytes using the mimic RNA sequence, LDH release was reduced, cell viability was enhanced, and apoptosis and necrosis rates were both decreased. By contrast, a deficiency in miR-24 resulted in the largest LDH release, lowest cell viability and highest apoptosis and necrosis rates in normal and ischemic myocytes, with significant changes compared to that of non-transfected myocytes. Additionally, the mRNA and protein levels of the pro-apoptotic gene, BCL2L11, were down-regulated by miR-24 overexpression and up-regulated by miR-24 deficiency. The luciferase reporter assay confirmed BCL2L11 to be a target of miR-24. Overall, this study showed a protective role for miR-24 against myocardial ischemia by inhibiting BCL2L11, and may represent a potential novel treatment for ischemic heart disease.

• MeSH
• apoptóza genetika   MeSH
• faktor 1 indukovatelný hypoxií metabolismus   MeSH
• ischemická choroba srdeční genetika   metabolismus   patologie   MeSH
• kardiomyocyty metabolismus   MeSH
• krysa rodu rattus MeSH
• L-laktátdehydrogenasa genetika   metabolismus   MeSH
• membránové proteiny genetika   metabolismus   MeSH
• mikro RNA genetika   metabolismus   MeSH
• nekróza genetika   MeSH
• ochranné látky metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• proteiny regulující apoptózu genetika   metabolismus   MeSH
• protoonkogenní proteiny genetika   metabolismus   MeSH
• upregulace MeSH
• viabilita buněk genetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The mechanisms of cell injury resulting in a special type of cell death combining the features of apoptosis and necrosis were examined in Hep-2 cells exposed to 300 µM zinc sulfate during 24h. Acute exposure to zinc induced a rapid rise in metallothionein levels and increased oxidative stress occurring in the absence of a significant early ATP depletion. Accentuated ATP loss and elevated levels of superoxide at later treatment intervals (12h and longer) were present along with increased DNA damage. Manipulation with ATP production and inhibition of NADPH oxidase had a positive effect on zinc-related increase in oxidative stress and influenced the observed type of cell death. These results suggest that Hep-2 cells acutely exposed to zinc increase intracellular labile zinc stores and over express metalothioneins. Elevated production of peroxides in zinc-treated cells is at later treatment intervals accompanied by an increase in superoxide levels, possibly by activation of NADPH oxidase, DNA damage and severe ATP loss. Prevention of critical ATP depletion and, in particular, inhibition of oxidative stress attenuates zinc-mediated cell injury and stimulates apoptosis-like phenotype in exposed cells.

• MeSH
• adenosintrifosfát chemie   nedostatek   MeSH
• apoptóza genetika   účinky léků   MeSH
• financování vládou MeSH
• lidé MeSH
• metalothionein chemie   MeSH
• NADPH-oxidasy fyziologie   genetika   imunologie   MeSH
• nekróza etiologie   genetika   chemicky indukované   MeSH
• oxidační stres genetika   imunologie   účinky léků   MeSH
• poškození DNA fyziologie   genetika   imunologie   MeSH
• zinek chemie   metabolismus   škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• srovnávací studie MeSH