A tumour suppressor miRNA, miR-128-3p, is widely involved in various biological processes and has been found to get downregulated in breast cancer patients. We previously published that ectopically expressed miR-128-3p suppressed migration, invasion, cell cycle arrest, and breast cancer stem cells. In the present study, we explored the role of Empagliflozin (EMPA) as a miR-128-3p functionality-mimicking drug in inducing ferroptosis by inhibiting CD98hc. Given that CD98hc is one of the proteins critical in triggering ferroptosis, we confirmed that miR-128-3p and EMPA inhibited SP1, leading to inhibition of CD98hc expression. Further, transfection with siCD98hc, miR-128-3p mimics, and inhibitors was performed to assess their involvement in the ferroptosis of anoikis-resistant cells. We proved that anoikis-resistant cells possess high ROS and iron levels. Further, miR-128-3p and EMPA treatments induced ferroptosis by inhibiting GSH and enzymatic activity of GPX4 and also induced lipid peroxidation. Moreover, EMPA suppressed bioluminescence of 4T1-Red-FLuc induced thoracic cavity, peritoneal tumour burden and lung nodules in an in-vivo metastatic model of breast cancer. Collectively, we revealed that EMPA sensitized the ECM detached cells to ferroptosis by synergically activating miR-128-3p and lowering the levels of SP1 and CD98hc, making it a potential adjunct drug for breast cancer chemotherapy.
- Klíčová slova
- 4T1 cells, Anoikis resistance, Breast cancer, Ferroptosis, Metastasis, Reactive oxygen species,
- MeSH
- anoikis * účinky léků genetika MeSH
- benzhydrylové sloučeniny * farmakologie MeSH
- ferroptóza * účinky léků genetika MeSH
- glifloziny farmakologie MeSH
- glukosidy * farmakologie MeSH
- kotransportní proteiny pro sodík a fosfát - typ IIb MeSH
- lidé MeSH
- mikro RNA * genetika metabolismus MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory prsu * patologie metabolismus farmakoterapie genetika MeSH
- peroxidace lipidů účinky léků MeSH
- reaktivní formy kyslíku metabolismus MeSH
- regulace genové exprese u nádorů * účinky léků MeSH
- xenogenní modely - testy antitumorózní aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- benzhydrylové sloučeniny * MeSH
- empagliflozin MeSH Prohlížeč
- glifloziny MeSH
- glukosidy * MeSH
- kotransportní proteiny pro sodík a fosfát - typ IIb MeSH
- mikro RNA * MeSH
- MIRN128 microRNA, human MeSH Prohlížeč
- reaktivní formy kyslíku MeSH
- SLC34A2 protein, human MeSH Prohlížeč
Nanobubble water promotes the degradation of difficult-to-degrade organic matter, improves the activity of electron transfer systems during anaerobic digestion, and optimizes the composition of anaerobic microbial communities. Therefore, this study proposes the use of nanobubble water to improve the yield of medium chain carboxylic acids produced from cow manure by chain elongation. The experiment was divided into two stages: the first stage involved the acidification of cow manure to produce volatile acidic fatty acids as electron acceptors, and the second phase involved the addition of lactic acid as an electron donor for the chain elongation. Three experimental groups were established, and air, H2, and N2 nanobubble water were added in the second stage. Equal amounts of deionized water were added in the control group. The results showed that nanobubble water supplemented with air significantly increased the caproic acid concentration to 15.10 g/L, which was 55.03 % greater than that of the control group. The relative abundances of Bacillus and Caproiciproducens, which are involved in chain elongation, and Syntrophomonas, which is involved in electron transfer, increased. The unique ability of air nanobubble water supplemented to break down the cellulose matrix resulted in further decomposition of the recalcitrant material in cow manure. This effect subsequently increased the number of microorganisms associated with lignocellulose degradation, increasing carbohydrate metabolism and ATP-binding cassette transporter protein activity and enhancing fatty acid cycling pathways during chain elongation. Ultimately, this approach enabled the efficient production of medium chain carboxylic acids.
- Klíčová slova
- Anaerobic digestion, Chain elongation, Electron transport, Fatty acid cycle pathway, Nanobubble water,
- MeSH
- anaerobióza MeSH
- biodegradace * MeSH
- Clostridiales MeSH
- dusík chemie MeSH
- hnůj * MeSH
- kyseliny karboxylové chemie MeSH
- kyseliny mastné těkavé chemie MeSH
- nanostruktury MeSH
- skot MeSH
- transport elektronů MeSH
- voda chemie MeSH
- vodík chemie MeSH
- vzduch MeSH
- zvířata MeSH
- Check Tag
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- dusík MeSH
- hnůj * MeSH
- kyseliny karboxylové MeSH
- kyseliny mastné těkavé MeSH
- lignocellulose MeSH Prohlížeč
- voda MeSH
- vodík MeSH
Our circadian world shapes much of metabolic physiology. In mice ∼40% of the light and ∼80% of the dark phase time is characterized by bouts of increased energy expenditure (EE). These ultradian bouts have a higher body temperature (Tb) and thermal conductance and contain virtually all of the physical activity and awake time. Bout status is a better classifier of mouse physiology than photoperiod, with ultradian bouts superimposed on top of the circadian light/dark cycle. We suggest that the primary driver of ultradian bouts is a brain-initiated transition to a higher defended Tb of the active/awake state. Increased energy expenditure from brown adipose tissue, physical activity, and cardiac work combine to raise Tb from the lower defended Tb of the resting/sleeping state. Thus, unlike humans, much of mouse metabolic physiology is episodic with large ultradian increases in EE and Tb that correlate with the active/awake state and are poorly aligned with circadian cycling.
- Klíčová slova
- Body temperature regulation, Brown adipose tissue, Contributors to energy expenditure, Physical activity and physical activity energy expenditure, Sleep/wake, Ultradian and circadian rhythms,
- MeSH
- bdění fyziologie MeSH
- cirkadiánní rytmus * fyziologie MeSH
- energetický metabolismus * fyziologie MeSH
- fotoperioda * MeSH
- hnědá tuková tkáň metabolismus fyziologie MeSH
- myši MeSH
- spánek fyziologie MeSH
- tělesná teplota * fyziologie MeSH
- ultradiánní rytmus * fyziologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Electroactive microorganisms are pivotal players in mineral transformation within redox interfaces characterized by pronounced oxygen and dissolved metal gradients. Yet, their systematic cultivation from such environments remains elusive. Here, we conducted an anodic enrichment using anoxic ferruginous waters from a post-mining lake as inoculum. Weak electrogenicity (j = ∼5 µA cm-2) depended on electroactive planktonic cells rather than anodic biofilms, with a preference for formate as electron donor. Addition of yeast extract decreased the lag phase but did not increase current densities. The enriched bacterial community varied depending on the substrate composition but mainly comprised of sulfate- and nitrate-reducing bacteria (e.g., Desulfatomaculum spp. and Stenotrophomonas spp.). A secondary enrichment strategy resulted in different bacterial communities composed of iron-reducing (e.g., Klebsiella spp.) and fermentative bacteria (e.g., Paeniclostridium spp.). Secondary electron microscopy and energy-dispersive X-ray spectroscopy results indicate the precipitation of sulfur- and iron-rich organomineral aggregates at the anode surface, presumably impeding current production. Our findings indicate that (i) anoxic waters containing geogenically derived metals can be used to enrich weak electricigens, and (ii) it is necessary to specifically inhibit sulfate reducers. Otherwise, sulfate reducers tend to dominate over EAM during cultivation, which can lead to anode passivation due to biomineralization.
- Klíčová slova
- Anodic Enrichment, Bioelectrochemical System, Biomineralization, Extracellular Electron Transfer, Ferruginous Lakes, Weak Electricigens,
- MeSH
- Bacteria MeSH
- jezera * mikrobiologie MeSH
- minerály MeSH
- oxidace-redukce MeSH
- sírany * MeSH
- železo chemie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- minerály MeSH
- sírany * MeSH
- železo MeSH
BACKGROUND & AIM: Dysfunction of skeletal muscle satellite cells might impair muscle regeneration and prolong ICU-acquired weakness, a condition associated with disability and delayed death. This study aimed to elucidate the distinct metabolic effects of critical illness and β-OH-butyrate on satellite cells isolated from these patients. METHODS: Satellite cells were extracted from vastus lateralis muscle biopsies of patients with ICU-acquired weakness (n = 10) and control group of healthy volunteers or patients undergoing elective hip replacement surgery (n = 10). The cells were exposed to standard culture media supplemented with β-OH-butyrate to assess its influence on cell proliferation by ELISA, mitochondrial functions by extracellular flux analysis, electron transport chain complexes by high resolution respirometry, and ROS production by confocal microscopy. RESULTS: Critical illness led to a decline in maximal respiratory capacity, ATP production and glycolytic capacity and increased ROS production in ICU patients' cells. Notably, the function of complex II was impaired due to critical illness but restored to normal levels upon exposure to β-OH-butyrate. While β-OH-butyrate significantly reduced ROS production in both control and ICU groups, it had no significant impact on global mitochondrial functions. CONCLUSION: Critical illness induces measurable bioenergetic dysfunction of skeletal muscle satellite cells. β-OH-butyrate displayed a potential in rectifying complex II dysfunction caused by critical illness and this warrants further exploration.
- Klíčová slova
- Critical illness, ICU-acquired muscle weakness, Mitochondria, Skeletal muscle cells, β-OH-butyrate,
- MeSH
- adenosintrifosfát metabolismus MeSH
- dospělí MeSH
- energetický metabolismus účinky léků MeSH
- kritický stav * MeSH
- kultivované buňky MeSH
- kyselina 3-hydroxymáselná * farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mitochondrie účinky léků metabolismus MeSH
- proliferace buněk účinky léků MeSH
- reaktivní formy kyslíku * metabolismus MeSH
- satelitní buňky kosterního svalu * účinky léků metabolismus MeSH
- senioři MeSH
- svalová slabost MeSH
- svalové mitochondrie účinky léků metabolismus 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
- adenosintrifosfát MeSH
- kyselina 3-hydroxymáselná * MeSH
- reaktivní formy kyslíku * MeSH
BACKGROUND: Amplification of HER2, a receptor tyrosine kinase and a breast cancer-linked oncogene, is associated with aggressive disease. HER2 protein is localised mostly at the cell membrane, but a fraction translocates to mitochondria. Whether and how mitochondrial HER2 contributes to tumorigenicity is currently unknown. METHODS: We enriched the mitochondrial (mt-)HER2 fraction in breast cancer cells using an N-terminal mitochondrial targeting sequence and analysed how this manipulation impacts bioenergetics and tumorigenic properties. The role of the tyrosine kinase activity of mt-HER2 was assessed in wild type, kinase-dead (K753M) and kinase-enhanced (V659E) mtHER2 constructs. RESULTS: We document that mt-HER2 associates with the oxidative phosphorylation system, stimulates bioenergetics and promotes larger respiratory supercomplexes. mt-HER2 enhances proliferation and invasiveness in vitro and tumour growth and metastatic potential in vivo, in a kinase activity-dependent manner. On the other hand, constitutively active mt-HER2 provokes excessive mitochondria ROS generation, sensitises to cell death, and restricts growth of primary tumours, suggesting that regulation of HER2 activity in mitochondria is required for the maximal pro-tumorigenic effect. CONCLUSIONS: mt-HER2 promotes tumorigenicity by supporting bioenergetics and optimal redox balance.
- Klíčová slova
- HER2, cancer, electron transport chain, mitochondria, reactive oxygen species,
- MeSH
- buněčné dýchání fyziologie MeSH
- energetický metabolismus MeSH
- karcinogeneze metabolismus MeSH
- lidé MeSH
- mitochondrie * metabolismus MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory prsu * metabolismus genetika MeSH
- oxidativní fosforylace MeSH
- proliferace buněk MeSH
- reaktivní formy kyslíku metabolismus MeSH
- receptor erbB-2 * metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
We present here the research contributions of Jan Amesz (1934-2001) on deciphering the details of the early physico-chemical steps in oxygenic photosynthesis in plants, algae and cyanobacteria, as well as in anoxygenic photosynthesis in purple, green, and heliobacteria. His research included light absorption and the mechanism of excitation energy transfer, primary photochemistry, and electron transfer steps until the reduction of pyridine nucleotides. Among his many discoveries, we emphasize his 1961 proof, with L. N. M. Duysens, of the "series scheme" of oxygenic photosynthesis, through antagonistic effects of Light I and II on the redox state of cytochrome f. Further, we highlight the following research on oxygenic photosynthesis: the experimental direct proof that plastoquinone and plastocyanin function at their respective places in the Z-scheme. In addition, Amesz's major contributions were in unraveling the mechanism of excitation energy transfer and electron transport steps in anoxygenic photosynthetic bacteria (purple, green and heliobacteria). Before we present his research, focusing on his key discoveries, we provide a glimpse of his personal life. We end this Tribute with reminiscences from three of his former doctoral students (Sigi Neerken; Hjalmar Pernentier, and Frank Kleinherenbrink) and from several scientists (Suleyman Allakhverdiev; Robert Blankenship; Richard Cogdell) including two of the authors (G. Garab and A. Stirbet) of this Tribute.
- Klíčová slova
- Chromatium sp., Rhodopseudomonas sp., Rhodospirillum sp, Anoxygenic photosynthesis, Bacteriochlorophyll, Carnegie Institute of Washington, Chlorophyll, Cytochrome f, Electron transfer, Excitation energy transfer, Heliobacteria, Louis (Lou) N.M. Duysens, Plastocyanin, Plastoquinone, Primary photochemistry, Reaction center, Two-electron gate, Winkler Prins prize, Z-scheme,
- MeSH
- biofyzika dějiny MeSH
- dějiny 20. století MeSH
- dějiny 21. století MeSH
- fotosyntéza * MeSH
- kyslík metabolismus MeSH
- transport elektronů MeSH
- Check Tag
- dějiny 20. století MeSH
- dějiny 21. století MeSH
- Publikační typ
- biografie MeSH
- časopisecké články MeSH
- historické články MeSH
- portréty MeSH
Plants have evolved multiple regulatory mechanisms to cope with natural light fluctuations. The interplay between these mechanisms leads presumably to the resilience of plants in diverse light patterns. We investigated the energy-dependent nonphotochemical quenching (qE) and cyclic electron transports (CET) in light that oscillated with a 60-s period with three different amplitudes. The photosystem I (PSI) and photosystem II (PSII) function-related quantum yields and redox changes of plastocyanin and ferredoxin were measured in Arabidopsis thaliana wild types and mutants with partial defects in qE or CET. The decrease in quantum yield of qE due to the lack of either PsbS- or violaxanthin de-epoxidase was compensated by an increase in the quantum yield of the constitutive nonphotochemical quenching. The mutant lacking NAD(P)H dehydrogenase (NDH)-like-dependent CET had a transient significant PSI acceptor side limitation during the light rising phase under high amplitude of light oscillations. The mutant lacking PGR5/PGRL1-CET restricted electron flows and failed to induce effective photosynthesis control, regardless of oscillation amplitudes. This suggests that PGR5/PGRL1-CET is important for the regulation of PSI function in various amplitudes of light oscillation, while NDH-like-CET acts' as a safety valve under fluctuating light with high amplitude. The results also bespeak interplays among multiple photosynthetic regulatory mechanisms.
- Klíčová slova
- alternative electron transports, cyclic electron transport, fluctuating light, rapidly reversible nonphotochemical quenching, regulation,
- MeSH
- Arabidopsis * fyziologie genetika účinky záření metabolismus MeSH
- ferredoxiny metabolismus MeSH
- fotosyntetické reakční centrum - proteinové komplexy metabolismus genetika MeSH
- fotosyntéza * fyziologie účinky záření MeSH
- fotosystém I - proteinový komplex * metabolismus MeSH
- fotosystém II - proteinový komplex * metabolismus MeSH
- membránové proteiny * MeSH
- mutace MeSH
- oxidace-redukce MeSH
- plastocyanin metabolismus MeSH
- proteiny huseníčku * metabolismus genetika MeSH
- světlo * MeSH
- transport elektronů MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ferredoxiny MeSH
- fotosyntetické reakční centrum - proteinové komplexy MeSH
- fotosystém I - proteinový komplex * MeSH
- fotosystém II - proteinový komplex * MeSH
- membránové proteiny * MeSH
- PGR5 protein, Arabidopsis MeSH Prohlížeč
- PGRL1 protein, Arabidopsis MeSH Prohlížeč
- plastocyanin MeSH
- proteiny huseníčku * MeSH
While endophytic fungi offer promising avenues for bolstering plant resilience against abiotic stressors, the molecular mechanisms behind this biofortification remain largely unknown. This study employed a multifaceted approach, combining plant physiology, proteomic, metabolomic, and targeted hormonal analyses to illuminate the early response of Brassica napus to Acremonium alternatum during the nascent stages of their interaction. Notably, under optimal growth conditions, the initial reaction to fungus was relatively subtle, with no visible alterations in plant phenotype and only minor impacts on the proteome and metabolome. Interestingly, the identified proteins associated with the Acremonium response included TUDOR 1, Annexin D4, and a plastidic K+ efflux antiporter, hinting at potential processes that could counter abiotic stressors, particularly salt stress. Subsequent experiments validated this hypothesis, showcasing significantly enhanced growth in Acremonium-inoculated plants under salt stress. Molecular analyses revealed a profound impact on the plant's proteome, with over 50% of salt stress response proteins remaining unaffected in inoculated plants. Acremonium modulated ribosomal proteins, increased abundance of photosynthetic proteins, enhanced ROS metabolism, accumulation of V-ATPase, altered abundances of various metabolic enzymes, and possibly promoted abscisic acid signaling. Subsequent analyses validated the accumulation of this hormone and its enhanced signaling. Collectively, these findings indicate that Acremonium promotes salt tolerance by orchestrating abscisic acid signaling, priming the plant's antioxidant system, as evidenced by the accumulation of ROS-scavenging metabolites and alterations in ROS metabolism, leading to lowered ROS levels and enhanced photosynthesis. Additionally, it modulates ion sequestration through V-ATPase accumulation, potentially contributing to the observed decrease in chloride content.
- MeSH
- Acremonium * metabolismus fyziologie MeSH
- Brassica napus mikrobiologie metabolismus fyziologie účinky léků MeSH
- fotosyntéza MeSH
- homeostáza * MeSH
- kyselina abscisová metabolismus MeSH
- oxidace-redukce * MeSH
- regulátory růstu rostlin * metabolismus MeSH
- rostlinné proteiny metabolismus genetika MeSH
- signální transdukce * MeSH
- solný stres fyziologie MeSH
- tolerance k soli * fyziologie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kyselina abscisová MeSH
- regulátory růstu rostlin * MeSH
- rostlinné proteiny MeSH
Activation of immune cells requires the remodeling of cell metabolism in order to support immune function. We study these metabolic changes through the infection of Drosophila larvae by parasitoid wasp. The parasitoid egg is neutralized by differentiating lamellocytes, which encapsulate the egg. A melanization cascade is initiated, producing toxic molecules to destroy the egg while the capsule also protects the host from the toxic reaction. We combined transcriptomics and metabolomics, including 13C-labeled glucose and trehalose tracing, as well as genetic manipulation of sugar metabolism to study changes in metabolism, specifically in Drosophila hemocytes. We found that hemocytes increase the expression of several carbohydrate transporters and accordingly uptake more sugar during infection. These carbohydrates are metabolized by increased glycolysis, associated with lactate production, and cyclic pentose phosphate pathway (PPP), in which glucose-6-phosphate is re-oxidized to maximize NADPH yield. Oxidative PPP is required for lamellocyte differentiation and resistance, as is systemic trehalose metabolism. In addition, fully differentiated lamellocytes use a cytoplasmic form of trehalase to cleave trehalose to glucose and fuel cyclic PPP. Intracellular trehalose metabolism is not required for lamellocyte differentiation, but its down-regulation elevates levels of reactive oxygen species, associated with increased resistance and reduced fitness. Our results suggest that sugar metabolism, and specifically cyclic PPP, within immune cells is important not only to fight infection but also to protect the host from its own immune response and for ensuring fitness of the survivor.
- MeSH
- buněčná diferenciace MeSH
- Drosophila melanogaster metabolismus parazitologie MeSH
- Drosophila metabolismus parazitologie MeSH
- glukosa * metabolismus MeSH
- glykolýza MeSH
- hemocyty * metabolismus MeSH
- interakce hostitele a parazita MeSH
- larva metabolismus parazitologie MeSH
- odolnost vůči nemocem MeSH
- pentózofosfátový cyklus * MeSH
- sršňovití metabolismus fyziologie MeSH
- trehalosa * metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH