Aerobic glycolysis is a prominent feature of cancer. Here, we reported that miR-19a-3p promotes aerobic glycolysis in ovarian cancer cells SKVO3 and ES-2 by increased production of ATP, lactic acid, extracellular acidification (ECAR), and increased expression of PKM2, LDHA, GLUT1 and GLUT3. Further study showed that over-expression of IGFBP3, the target of miR-19a-3p, decreases aerobic glycolysis in ovarian cancer cells, while knockdown of IGFBP3 expression increases aerobic glycolysis. The rescue assay suggested that miR-19a-3p promotes aerobic glycolysis in ovarian cancer cells through targeting IGFBP3. Moreover, over-expression of miR-19a-3p or silencing of IGFBP3 expression promoted activation of AKT, which is important for aerobic glycolysis in cancer cells, indicating that miR-19a-3p promotes aerobic glycolysis in ovarian cancer cells through the IGFBP3/PI3K/AKT pathway. This suggests that miR-19a-3p and IGFBP3 may serve as potential treatment targets of ovarian cancer.
- MeSH
- fosfatidylinositol-3-kinasy metabolismus MeSH
- glykolýza genetika MeSH
- IGFBP-3 genetika metabolismus MeSH
- lidé MeSH
- mikro RNA * genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- nádory vaječníků * genetika MeSH
- proliferace buněk MeSH
- protoonkogenní proteiny c-akt metabolismus MeSH
- regulace genové exprese u nádorů MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The main bottleneck in the return of industrial butanol production from renewable feedstock through acetone-butanol-ethanol (ABE) fermentation by clostridia, such as Clostridium beijerinckii, is the low final butanol concentration. The problem is caused by the high toxicity of butanol to the production cells, and therefore, understanding the mechanisms by which clostridia react to butanol shock is of key importance. Detailed analyses of transcriptome data that were obtained after butanol shock and their comparison with data from standard ABE fermentation have resulted in new findings, while confirmed expected population responses. Although butanol shock resulted in upregulation of heat shock protein genes, their regulation is different than was assumed based on standard ABE fermentation transcriptome data. While glucose uptake, glycolysis, and acidogenesis genes were downregulated after butanol shock, solventogenesis genes were upregulated. Cyclopropanation of fatty acids and formation of plasmalogens seem to be significant processes involved in cell membrane stabilization in the presence of butanol. Surprisingly, one of the three identified Agr quorum-sensing system genes was upregulated. Upregulation of several putative butanol efflux pumps was described after butanol addition and a large putative polyketide gene cluster was found, the transcription of which seemed to depend on the concentration of butanol.
- MeSH
- biologický transport genetika MeSH
- bioreaktory mikrobiologie MeSH
- buněčná membrána metabolismus MeSH
- butanoly toxicita MeSH
- Clostridium beijerinckii účinky léků genetika metabolismus MeSH
- fyziologický stres genetika MeSH
- glukosa metabolismus MeSH
- glykolýza genetika fyziologie MeSH
- mastné kyseliny metabolismus MeSH
- plasmalogeny biosyntéza MeSH
- proteiny tepelného šoku metabolismus MeSH
- quorum sensing genetika MeSH
- stanovení celkové genové exprese MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Although the modulation of host physiology has been interpreted as an essential process supporting baculovirus propagation, the requirement of energy supply for host antivirus reactions could not be ruled out. Our present study showed that metabolic induction upon AcMNPV (budded virus) infection of Bombyx mori stimulated virus clearance and production of the antivirus protein, gloverin. In addition, we demonstrated that adenosine receptor signaling (AdoR) played an important role in regulating such metabolic reprogramming upon baculovirus infection. By using a second lepidopteran model, Spodoptera frugiperda Sf-21 cells, we demonstrated that the glycolytic induction regulated by adenosine signaling was a conservative mechanism modulating the permissiveness of baculovirus infection. Another interesting finding in our present study is that both BmNPV and AcMNPV infection cause metabolic activation, but it appears that BmNPV infection moderates the level of ATP production, which is in contrast to a dramatic increase upon AcMNPV infection. We identified potential AdoR miRNAs induced by BmNPV infection and concluded that BmNPV may attempt to minimize metabolic activation by suppressing adenosine signaling and further decreasing the host's anti-baculovirus response. Our present study shows that activation of energy synthesis by adenosine signaling upon baculovirus infection is a host physiological response that is essential for supporting the innate immune response against infection.
- MeSH
- adenosin metabolismus MeSH
- adenosintrifosfát biosyntéza MeSH
- bourec metabolismus virologie MeSH
- deoxyglukosa farmakologie MeSH
- energetický metabolismus MeSH
- glykolýza účinky léků genetika MeSH
- hmyzí proteiny metabolismus MeSH
- infekce DNA virem metabolismus virologie MeSH
- interakce hostitele a patogenu imunologie MeSH
- mezibuněčné signální peptidy a proteiny metabolismus MeSH
- nukleopolyhedroviry fyziologie MeSH
- purinergní receptory P1 genetika metabolismus MeSH
- replikace viru účinky léků MeSH
- Sf9 buňky MeSH
- Spodoptera MeSH
- transfekce MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The obligate intracellular pathogen, Anaplasma phagocytophilum, is the causative agent of human, equine, and canine granulocytic anaplasmosis and tick-borne fever (TBF) in ruminants. A. phagocytophilum has become an emerging tick-borne pathogen in the United States, Europe, Africa, and Asia, with increasing numbers of infected people and animals every year. It has been recognized that intracellular pathogens manipulate host cell metabolic pathways to increase infection and transmission in both vertebrate and invertebrate hosts. However, our current knowledge on how A. phagocytophilum affect these processes in the tick vector, Ixodes scapularis is limited. In this study, a genome-wide search for components of major carbohydrate metabolic pathways was performed in I. scapularis ticks for which the genome was recently published. The enzymes involved in the seven major carbohydrate metabolic pathways glycolysis, gluconeogenesis, pentose phosphate, tricarboxylic acid cycle (TCA), glyceroneogenesis, and mitochondrial oxidative phosphorylation and β-oxidation were identified. Then, the available transcriptomics and proteomics data was used to characterize the mRNA and protein levels of I. scapularis major carbohydrate metabolic pathway components in response to A. phagocytophilum infection of tick tissues and cultured cells. The results showed that major carbohydrate metabolic pathways are conserved in ticks. A. phagocytophilum infection inhibits gluconeogenesis and mitochondrial metabolism, but increases the expression of glycolytic genes. A model was proposed to explain how A. phagocytophilum could simultaneously control tick cell glucose metabolism and cytoskeleton organization, which may be achieved in part by up-regulating and stabilizing hypoxia inducible factor 1 alpha in a hypoxia-independent manner. The present work provides a more comprehensive view of the major carbohydrate metabolic pathways involved in the response to A. phagocytophilum infection in ticks, and provides the basis for further studies to develop novel strategies for the control of granulocytic anaplasmosis.
- MeSH
- Anaplasma phagocytophilum patogenita fyziologie MeSH
- anaplasmóza metabolismus MeSH
- buněčné linie MeSH
- citrátový cyklus genetika MeSH
- glukoneogeneze genetika MeSH
- glykolýza genetika MeSH
- interakce hostitele a patogenu genetika MeSH
- klíště enzymologie genetika metabolismus mikrobiologie MeSH
- metabolické sítě a dráhy genetika MeSH
- metabolismus sacharidů genetika MeSH
- mitochondrie genetika metabolismus MeSH
- pentózofosfátový cyklus genetika MeSH
- proteiny členovců chemie genetika metabolismus MeSH
- proteomika metody MeSH
- regulace genové exprese fyziologie MeSH
- sacharidy MeSH
- slinné žlázy mikrobiologie MeSH
- terciární struktura proteinů MeSH
- transkriptom genetika MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Glycolytic shift is a characteristic feature of rapidly proliferating cells, such as cells during development and during immune response or cancer cells, as well as of stem cells. It results in increased glycolysis uncoupled from mitochondrial respiration, also known as the Warburg effect. Notch signalling is active in contexts where cells undergo glycolytic shift. We decided to test whether metabolic genes are direct transcriptional targets of Notch signalling and whether upregulation of metabolic genes can help Notch to induce tissue growth under physiological conditions and in conditions of Notch-induced hyperplasia. We show that genes mediating cellular metabolic changes towards the Warburg effect are direct transcriptional targets of Notch signalling. They include genes encoding proteins involved in glucose uptake, glycolysis, lactate to pyruvate conversion and repression of the tricarboxylic acid cycle. The direct transcriptional upregulation of metabolic genes is PI3K/Akt independent and occurs not only in cells with overactivated Notch but also in cells with endogenous levels of Notch signalling and in vivo. Even a short pulse of Notch activity is able to elicit long-lasting metabolic changes resembling the Warburg effect. Loss of Notch signalling in Drosophila wing discs as well as in human microvascular cells leads to downregulation of glycolytic genes. Notch-driven tissue overgrowth can be rescued by downregulation of genes for glucose metabolism. Notch activity is able to support growth of wing during nutrient-deprivation conditions, independent of the growth of the rest of the body. Notch is active in situations that involve metabolic reprogramming, and the direct regulation of metabolic genes may be a common mechanism that helps Notch to exert its effects in target tissues.
- MeSH
- aktivace transkripce MeSH
- biologické modely MeSH
- buněčné linie MeSH
- citrátový cyklus genetika MeSH
- energetický metabolismus genetika MeSH
- exprese genu MeSH
- glykolýza genetika MeSH
- lidé MeSH
- promotorové oblasti (genetika) MeSH
- proteiny Drosophily genetika metabolismus MeSH
- receptory Notch genetika metabolismus MeSH
- regulace genové exprese * MeSH
- regulační oblasti nukleových kyselin MeSH
- reportérové geny MeSH
- represorové proteiny genetika metabolismus MeSH
- vazba proteinů MeSH
- vazebná místa MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Physical processes in living cells were not taken into consideration among the essentials of biological activity, regardless of the fact that they establish a state far from thermodynamic equilibrium. In biological system chemical energy is transformed into the work of physical forces for various biological functions. The energy transformation pathway is very likely connected with generation of the endogenous electrodynamic field as suggested by experimentally proved electrodynamic activity of biological systems connected with mitochondrial and microtubule functions. Besides production of ATP and GTP (adenosine and guanosine triphosphate) mitochondria form a proton space charge layer,
- MeSH
- adenosintrifosfát metabolismus MeSH
- apoptóza fyziologie genetika imunologie MeSH
- biomedicínský výzkum metody trendy MeSH
- elektromagnetická pole škodlivé účinky MeSH
- financování organizované MeSH
- fyziologie buňky fyziologie genetika imunologie MeSH
- glykolýza fyziologie genetika imunologie MeSH
- guanosintrifosfát metabolismus MeSH
- kyselina dichloroctová aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- mikrotubuly fyziologie metabolismus patologie MeSH
- mitochondrie fyziologie metabolismus patologie MeSH
- nádorová transformace buněk genetika imunologie účinky léků MeSH
- nádory etiologie metabolismus terapie MeSH
- Check Tag
- lidé MeSH
Gene duplication is an important evolutionary mechanism and no eukaryote has more duplicated gene families than the parasitic protist Trichomonas vaginalis. Iron is an essential nutrient for Trichomonas and plays a pivotal role in the establishment of infection, proliferation, and virulence. To gain insight into the role of iron in T. vaginalis gene expression and genome evolution, we screened iron-regulated genes using an oligonucleotide microarray for T. vaginalis and by comparative EST (expressed sequence tag) sequencing of cDNA libraries derived from trichomonads cultivated under iron-rich (+Fe) and iron-restricted (-Fe) conditions. Among 19,000 ESTs from both libraries, we identified 336 iron-regulated genes, of which 165 were upregulated under +Fe conditions and 171 under -Fe conditions. The microarray analysis revealed that 195 of 4,950 unique genes were differentially expressed. Of these, 117 genes were upregulated under +Fe conditions and 78 were upregulated under -Fe conditions. The results of both methods were congruent concerning the regulatory trends and the representation of gene categories. Under +Fe conditions, the expression of proteins involved in carbohydrate metabolism, particularly in the energy metabolism of hydrogenosomes, and in methionine catabolism was increased. The iron-sulfur cluster assembly machinery and certain cysteine proteases are of particular importance among the proteins upregulated under -Fe conditions. A unique feature of the T. vaginalis genome is the retention during evolution of multiple paralogous copies for a majority of all genes. Although the origins and reasons for this gene expansion remain unclear, the retention of multiple gene copies could provide an opportunity to evolve differential expression during growth in variable environmental conditions. For genes whose expression was affected by iron, we found that iron influenced the expression of only some of the paralogous copies, whereas the expression of the other paralogs was iron independent. This finding indicates a very stringent regulation of the differentially expressed paralogous genes in response to changes in the availability of exogenous nutrients and provides insight into the evolutionary rationale underlying massive paralog retention in the Trichomonas genome.
- MeSH
- cysteinové proteasy genetika metabolismus MeSH
- duplikace genu MeSH
- exprimované sekvenční adresy MeSH
- genom protozoální MeSH
- genová dávka MeSH
- genová knihovna MeSH
- glykolýza genetika MeSH
- molekulární evoluce MeSH
- proteiny obsahující železo a síru genetika metabolismus MeSH
- protozoální geny * MeSH
- regulace genové exprese * MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- transkriptom * MeSH
- Trichomonas vaginalis genetika metabolismus MeSH
- železo metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A decrease in oxidative phosphorylation (OXPHOS) is characteristic of many cancer types and, in particular, of clear cell renal carcinoma (CCRC) deficient in von Hippel-Lindau (vhl) gene. In the absence of functional pVHL, hypoxia-inducible factor (HIF) 1-alpha and HIF2-alpha subunits are stabilized, which induces the transcription of many genes including those involved in glycolysis and reactive oxygen species (ROS) metabolism. Transfection of these cells with vhl is known to restore HIF-alpha subunit degradation and to reduce glycolytic genes transcription. We show that such transfection with vhl of 786-0 CCRC (which are devoid of HIF1-alpha) also increased the content of respiratory chain subunits. However, the levels of most transcripts encoding OXPHOS subunits were not modified. Inhibition of HIF2-alpha synthesis by RNA interference in pVHL-deficient 786-0 CCRC also restored respiratory chain subunit content and clearly demonstrated a key role of HIF in OXPHOS regulation. In agreement with these observations, stabilization of HIF-alpha subunit by CoCl(2) decreased respiratory chain subunit levels in CCRC cells expressing pVHL. In addition, HIF stimulated ROS production and mitochondrial manganese superoxide dismutase content. OXPHOS subunit content was also decreased by added H(2)O(2.) Interestingly, desferrioxamine (DFO) that also stabilized HIF did not decrease respiratory chain subunit level. While CoCl(2) significantly stimulates ROS production, DFO is known to prevent hydroxyl radical production by inhibiting Fenton reactions. This indicates that the HIF-induced decrease in OXPHOS is at least in part mediated by hydroxyl radical production.
- MeSH
- deferoxamin farmakologie MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa * genetika metabolismus MeSH
- glykolýza genetika MeSH
- homeostáza MeSH
- kobalt farmakologie MeSH
- lidé MeSH
- nádory genetika MeSH
- oxidativní fosforylace * MeSH
- peroxid vodíku farmakologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- reaktivní formy kyslíku * metabolismus MeSH
- receptory aromatických uhlovodíků - jaderný translokátor * genetika metabolismus MeSH
- respirační vzplanutí fyziologie účinky léků MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- transportní proteiny genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
