Recognition of pathogen-associated molecular patterns (PAMPs) is crucial for plant defence against pathogen attack. The best characterized PAMP is flg22, a 22 amino acid conserved peptide from flagellin protein. In Arabidopsis thaliana, flg22 is recognized by the flagellin sensing 2 (FLS2) receptor. In this study, we focused on biotic stress responses triggered by flg22 after exposure to temporary heat stress (HS). It is important to study the reactions of plants to multiple stress conditions because plants are often exposed simultaneously to a combination of both abiotic and biotic stresses. Transient early production of reactive oxygen species (ROS) is a well-characterized response to PAMP recognition. We demonstrate the strong reduction of flg22-induced ROS production in A. thaliana after HS treatment. In addition, a decrease in FLS2 transcription and a decrease of the FLS2 presence at the plasma membrane are shown after HS. In summary, our data show the strong inhibitory effect of HS on flg22-triggered events in A. thaliana. Subsequently, temporary HS strongly decreases the resistance of A. thaliana to Pseudomonas syringae. We propose that short exposure to high temperature is a crucial abiotic stress factor that suppresses PAMP-triggered immunity, which subsequently leads to the higher susceptibility of plants to pathogens.
- MeSH
- alarminy metabolismus MeSH
- Arabidopsis účinky léků genetika imunologie mikrobiologie MeSH
- flagelin farmakologie MeSH
- genetická transkripce účinky léků MeSH
- imunita rostlin * účinky léků MeSH
- nemoci rostlin imunologie mikrobiologie MeSH
- odolnost vůči nemocem imunologie MeSH
- proteiny huseníčku genetika metabolismus MeSH
- Pseudomonas syringae účinky léků fyziologie MeSH
- reakce na tepelný šok * účinky léků MeSH
- regulace genové exprese u rostlin účinky léků MeSH
- respirační vzplanutí účinky léků MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Cytokinins are phytohormones that are involved in many processes in plants, including growth, differentiation and leaf senescence. However, they also have various activities in animals. For example, kinetin and trans-zeatin can reduce levels of several aging markers in human fibroblasts. Kinetin can also protect mice against oxidative and glyoxidative stress, and prolong fruit flies' lifespan. Additionally, several cytokinins are currently used in cosmetics. To extend knowledge of the breadth of cytokinins' activities, we examined effects of natural cytokinin bases on the model nematode Caenorhabditis elegans. We found that kinetin, para-topolin and meta-topolin prolonged the lifespan of C. elegans. Kinetin also protected the organism against oxidative and heat stress. Furthermore, our results suggest that presence of reactive oxygen species, but not DAF-16 (the main effector of the insulin/insulin-like growth factor signaling pathway), is required for the beneficial effects of kinetin. Ultra-high performance liquid chromatography-tandem mass spectrometric analysis showed that kinetin is unlikely to occur naturally in C. elegans, but the worm efficiently absorbs and metabolizes it into kinetin riboside and kinetin riboside-5'-monophosphate.
- MeSH
- Caenorhabditis elegans účinky léků genetika fyziologie MeSH
- cytokininy farmakokinetika farmakologie MeSH
- dlouhověkost účinky léků fyziologie MeSH
- forkhead transkripční faktory genetika metabolismus MeSH
- inzulin metabolismus MeSH
- kinetin farmakokinetika farmakologie MeSH
- mutace MeSH
- oxidační stres účinky léků MeSH
- proteiny Caenorhabditis elegans genetika metabolismus MeSH
- reakce na tepelný šok účinky léků MeSH
- reaktivní formy kyslíku metabolismus MeSH
- regulátory růstu rostlin farmakokinetika farmakologie MeSH
- signální transdukce účinky léků MeSH
- termotolerance účinky léků MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Cancer incidence is rising and this global challenge is further exacerbated by tumour resistance to available medicines. A promising approach to meet the need for improved cancer treatment is drug repurposing. Here we highlight the potential for repurposing disulfiram (also known by the trade name Antabuse), an old alcohol-aversion drug that has been shown to be effective against diverse cancer types in preclinical studies. Our nationwide epidemiological study reveals that patients who continuously used disulfiram have a lower risk of death from cancer compared to those who stopped using the drug at their diagnosis. Moreover, we identify the ditiocarb-copper complex as the metabolite of disulfiram that is responsible for its anti-cancer effects, and provide methods to detect preferential accumulation of the complex in tumours and candidate biomarkers to analyse its effect on cells and tissues. Finally, our functional and biophysical analyses reveal the molecular target of disulfiram's tumour-suppressing effects as NPL4, an adaptor of p97 (also known as VCP) segregase, which is essential for the turnover of proteins involved in multiple regulatory and stress-response pathways in cells.
- MeSH
- alkoholismus farmakoterapie epidemiologie MeSH
- cílená molekulární terapie MeSH
- disulfiram chemie farmakologie terapeutické užití MeSH
- dospělí MeSH
- jaderné proteiny chemie metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- měď chemie MeSH
- myši MeSH
- nádory farmakoterapie metabolismus mortalita patologie MeSH
- odvykací prostředky alkoholu * farmakologie terapeutické užití MeSH
- přehodnocení terapeutických indikací léčivého přípravku * MeSH
- proteinové agregáty MeSH
- proteolýza účinky léků MeSH
- protinádorové látky * farmakologie terapeutické užití MeSH
- reakce na tepelný šok účinky léků MeSH
- vazba proteinů účinky léků MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Dánsko epidemiologie MeSH
To investigate the role of mitochondrial antioxidant capacity during increased susceptibility to heat accompanied by the aging, young and aged Wistar rats were exposed on heat for 60 min. After heat exposure, hepatic and brain mitochondria were isolated. Our results revealed changes in antioxidant enzyme activities in liver and brain mitochondria from young and to a greater extent in aged rats. Our measurements of MnSOD, GPx and GR activity indicate greater reactive oxygen species production from the mitochondria of aged heat exposed in comparison to young heat exposed rats. Also in the aged rats, the effect of alpha-tocopherol treatment in the prevention of oxidative stress occurred as a result of heat exposure, is less pronounced. Taken together, our data suggest that mitochondria in aged rats are more vulnerable and less able to prevent oxidative changes that occur in response to acute heat exposure.
- MeSH
- alfa-tokoferol farmakologie MeSH
- antioxidancia farmakologie MeSH
- časové faktory MeSH
- enzymy metabolismus MeSH
- glutathionperoxidasa metabolismus MeSH
- glutathionreduktasa metabolismus MeSH
- jaterní mitochondrie účinky léků enzymologie MeSH
- krysa rodu rattus MeSH
- mitochondrie účinky léků enzymologie MeSH
- mozek účinky léků enzymologie MeSH
- oxidační stres účinky léků MeSH
- potkani Wistar MeSH
- reakce na tepelný šok účinky léků MeSH
- stárnutí metabolismus MeSH
- superoxiddismutasa metabolismus MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Small ubiquitin-related modifiers 1, 2 and 3 (SUMO-1, -2, -3), members of the ubiquitin-like protein family, can be conjugated to various cellular proteins. Conjugates of SUMO-2 and SUMO-3 (SUMO-2/3) accumulate in cells exposed to various stress stimuli or to MG132 treatment. Although the proteins modified by SUMO-2/3 during heat shock or under MG132 treatment have been identified, the significance of this modification remains unclear. Our data show that the inhibition of translation by puromycin or cycloheximide blocks both the heat shock and MG132 induced accumulation of SUMO-2/3 conjugates in HEK 293T and U2OS cells. However, the heat shock induced accumulation of SUMO-2/3 conjugates was restored by proteasome inhibition, which suggests that the inhibition of translation did not abolish SUMOylation itself. Furthermore, we show that some of the proteins truncated due to the treatment by low concentration of puromycin are SUMOylated in HEK 293T cells. We suggest that the SUMO-2/3 conjugates accumulating under the heat shock or MG132 treatment result largely from new protein synthesis and that portion of them is incorrectly folded.
- MeSH
- benzochinony farmakologie MeSH
- biologické modely MeSH
- cykloheximid farmakologie MeSH
- HEK293 buňky MeSH
- HeLa buňky MeSH
- inhibitory syntézy proteinů farmakologie MeSH
- leupeptiny farmakologie MeSH
- lidé MeSH
- makrocyklické laktamy farmakologie MeSH
- malé modifikační proteiny související s ubikvitinem metabolismus MeSH
- proteasomový endopeptidasový komplex metabolismus MeSH
- proteosyntéza účinky léků MeSH
- puromycin farmakologie MeSH
- reakce na tepelný šok účinky léků MeSH
- sumoylace účinky léků MeSH
- ubikvitiny metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- chinony antagonisté a inhibitory farmakokinetika imunologie MeSH
- estradiol farmakokinetika imunologie MeSH
- eukaryotické buňky cytologie účinky léků MeSH
- finanční podpora výzkumu jako téma MeSH
- kvasinky účinky léků MeSH
- prednisolon antagonisté a inhibitory farmakokinetika imunologie MeSH
- proteiny tepelného šoku HSP90 analýza farmakokinetika MeSH
- reakce na tepelný šok fyziologie imunologie účinky léků MeSH
- rifabutin antagonisté a inhibitory farmakokinetika imunologie MeSH
- Publikační typ
- srovnávací studie MeSH
