Monohydroxylated PCBs (OH-PCBs) are an (eco)toxicologically significant group of compounds, as they arise from the oxidation of polychlorinated biphenyls (PCBs) and, at the same time, may exert even more severe toxic effects than their parent PCB molecules. Despite having been widely detected in environmental samples, plants, and animals, information on the fate of OH-PCBs in the environment is scarce, including on the enzymatic machinery behind their degradation. To date, only a few bacterial taxa capable of OH-PCB transformation have been reported. In this study, we aimed to obtain a deeper insight into the transformation of OH-PCBs in soil bacteria and isolated a Pseudomonas sp. strain P1B16 based on its ability to use o-phenylphenol (2-PP) which, when exposed to the Delor 103-derived OH-PCB mixture, depleted a wide spectrum of mono-, di, and trichlorinated OH-PCBs. In the P1B16 genome, a region designated as hbp was identified, which bears a set of putative genes involved in the transformation of OH-PCBs, namely hbpA encoding for a putative flavin-dependent 2-hydroxybiphenyl monooxygenase, hbpC (2,3-dihydroxybiphenyl-1,2-dioxygenase), hbpD (2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate hydrolase), and the transcriptional activator-encoding gene hbpR. The hbpA coding sequence was heterologously expressed, purified, and its substrate specificity was investigated towards the Delor 103-derived OH-PCB mixture, individual OH-PCBs, and multiple (chlorinated) phenolics. Apart from 2-PP and 2-chlorophenol, HbpA was also demonstrated to transform a range of OH-PCBs, including a 3-hydroxy-2,2',4',5,5'-pentachlorobiphenyl. Importantly, this is the first direct evidence of HbpA homologs being involved in the degradation of OH-PCBs. Moreover, using a P1B16-based biosensor strain, the specific induction of hbp genes by 2-PP, 3-phenylphenol, 4-phenylphenol, and the OH-PCB mixture was demonstrated. This study provides direct evidence on the specific enzymatic machinery responsible for the transformation of OH-PCBs in bacteria, with many implications in ecotoxicology, environmental restoration, and microbial ecology in habitats burdened with PCB contamination.
- Klíčová slova
- 2-Hydroxybiphenyl 3-monooxygenase, Biodegradation of xenobiotics, Ecotoxicology, Hydroxylated polychlorinated biphenyls,
- MeSH
- Bacteria metabolismus MeSH
- hydroxylace MeSH
- oxygenasy se smíšenou funkcí metabolismus MeSH
- polychlorované bifenyly * metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 2-hydroxybiphenyl 3-monooxygenase MeSH Prohlížeč
- 2,4',5-trichlorobiphenyl MeSH Prohlížeč
- oxygenasy se smíšenou funkcí MeSH
- polychlorované bifenyly * MeSH
Ceramides (Cers) with α-hydroxylated acyl chains comprise about a third of all extractable skin Cers and are required for permeability barrier homeostasis. We have probed here the effects of Cer hydroxylation on their behavior in lipid models comprising the major SC lipids, Cer/free fatty acids (C 16-C 24)/cholesterol, and a minor component, cholesteryl sulfate. Namely, Cers with (R)-α-hydroxy lignoceroyl chains attached to sphingosine (Cer AS), dihydrosphingosine (Cer AdS), and phytosphingosine (Cer AP) were compared to their unnatural (S)-diastereomers and to Cers with non-hydroxylated lignoceroyl chains attached to sphingosine (Cer NS), dihydrosphingosine (Cer NdS), and phytosphingosine (Cer NP). By comparing several biophysical parameters (lamellar organization by X-ray diffraction, chain order, lateral packing, phase transitions, and lipid mixing by infrared spectroscopy using deuterated lipids) and the permeabilities of these models (water loss and two permeability markers), we conclude that there is no general or common consequence of Cer α-hydroxylation. Instead, we found a rich mix of effects, highly dependent on the sphingoid base chain, configuration at the α-carbon, and permeability marker used. We found that the model membranes with unnatural Cer (S)-AS have fewer orthorhombically packed lipid chains than those based on the (R)-diastereomer. In addition, physiological (R)-configuration decreases the permeability of membranes, with Cer (R)-AdS to theophylline, and increases the lipid chain order in model systems with natural Cer (R)-AP. Thus, each Cer subclass makes a distinct contribution to the structural organization and function of the skin lipid barrier.
- Klíčová slova
- biophysics, ceramides, hydroxylation, lipids, permeability, skin barrier, stratum corneum,
- MeSH
- acylace MeSH
- ceramidy chemie MeSH
- hydroxylace MeSH
- kůže chemie metabolismus MeSH
- lidé MeSH
- permeabilita MeSH
- sfingosin analogy a deriváty chemie MeSH
- změna skupenství * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ceramidy MeSH
- phytosphingosine MeSH Prohlížeč
- safingol MeSH Prohlížeč
- sfingosin MeSH
The patients with mantle cell lymphoma (MCL) have translocation t(11;14) associated with cyclin D1 overexpression. We observed that iron (an essential cofactor of dioxygenases including prolyl hydroxylases [PHDs]) depletion by deferoxamine blocked MCL cells' proliferation, increased expression of DNA damage marker γH2AX, induced cell cycle arrest and decreased cyclin D1 level. Treatment of MCL cell lines with dimethyloxalylglycine, which blocks dioxygenases involving PHDs by competing with their substrate 2-oxoglutarate, leads to their decreased proliferation and the decrease of cyclin D1 level. We then postulated that loss of EGLN2/PHD1 in MCL cells may lead to down-regulation of cyclin D1 by blocking the degradation of FOXO3A, a cyclin D1 suppressor. However, the CRISPR/Cas9-based loss-of-function of EGLN2/PHD1 did not affect cyclin D1 expression and the loss of FOXO3A did not restore cyclin D1 levels after iron chelation. These data suggest that expression of cyclin D1 in MCL is not controlled by ENGL2/PHD1-FOXO3A pathway and that chelation- and 2-oxoglutarate competition-mediated down-regulation of cyclin D1 in MCL cells is driven by yet unknown mechanism involving iron- and 2-oxoglutarate-dependent dioxygenases other than PHD1. These data support further exploration of the use of iron chelation and 2-oxoglutarate-dependent dioxygenase inhibitors as a novel therapy of MCL.
- Klíčová slova
- 2-oxoglutarate-dependent enzymes, DNA damage, cell cycle, iron, mantle cell lymphoma, prolyl hydroxylases (EGLN/PHDs),
- MeSH
- aminokyseliny dikarboxylové farmakologie MeSH
- chelátory železa farmakologie MeSH
- cyklin D1 metabolismus MeSH
- deferoxamin farmakologie MeSH
- deficit železa MeSH
- dioxygenasy antagonisté a inhibitory metabolismus MeSH
- down regulace účinky léků MeSH
- hydroxylace MeSH
- hypoxie buňky účinky léků MeSH
- inhibitory enzymů farmakologie MeSH
- kyseliny ketoglutarové farmakologie MeSH
- lidé MeSH
- lymfom z plášťových buněk enzymologie MeSH
- messenger RNA genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- poškození DNA MeSH
- prolyl-4-hydroxylasy HIF metabolismus MeSH
- protein FOXO3 genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- aminokyseliny dikarboxylové MeSH
- chelátory železa MeSH
- cyklin D1 MeSH
- deferoxamin MeSH
- dioxygenasy MeSH
- EGLN2 protein, human MeSH Prohlížeč
- FOXO3 protein, human MeSH Prohlížeč
- inhibitory enzymů MeSH
- kyseliny ketoglutarové MeSH
- messenger RNA MeSH
- oxalylglycine MeSH Prohlížeč
- prolyl-4-hydroxylasy HIF MeSH
- protein FOXO3 MeSH
Ceramides (Cers) are significant constituents of the stratum corneum (SC), the uppermost skin layer responsible for skin barrier properties. Cers are a heterogeneous group of lipids whose mutual interactions are still unclear. To better understand these interactions, we characterized model membranes containing stearic acid, cholesterol, cholesterol sulfate and one or more of the following ceramides: N-stearoyl-sphingosine (CerNS), N-stearoyl-phytosphingosine (CerNP) and N-(2-hydroxy)stearoyl-phytosphingosine (CerAP). Small angle X-ray scattering and FTIR spectroscopy were used to study lipid arrangement, phase separation and thermotropic behaviour. In the one-Cer systems, the membranes with CerNP showed strong hydrogen bonding and significant phase separation, even after phase transition, while the systems containing CerAP and CerNS had increased lipid miscibility. The multi-Cer systems exhibited different behaviour. In particular, the membrane containing all three Cers was a highly miscible system with narrow one-step phase transition, which, of all the studied samples, occurred at the lowest temperatures. Our results show that even a small variation in Cer structure results in substantially different phase behaviour, which is further affected by the presence of other Cer subclasses. Interestingly, the phase behaviour of the most complex three-Cer system was simpler than that of the others, highlighting the importance of lipid diversity in real SC.
- Klíčová slova
- Ceramides, FTIR, Model membranes, Skin delivery, Stratum corneum lipids, X-ray scattering,
- MeSH
- ceramidy chemie MeSH
- hydroxylace MeSH
- kůže chemie MeSH
- membránové lipidy chemie MeSH
- sfingosin analogy a deriváty chemie MeSH
- teplota MeSH
- změna skupenství MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ceramidy MeSH
- membránové lipidy MeSH
- phytosphingosine MeSH Prohlížeč
- sfingosin MeSH
The mechanisms contributing to toxic effects of airborne lower-chlorinated PCB congeners (LC-PCBs) remain poorly characterized. We evaluated in vitro toxicities of environmental LC-PCBs found in both indoor and outdoor air (PCB 4, 8, 11, 18, 28 and 31), and selected hydroxylated metabolites of PCB 8, 11 and 18, using reporter gene assays, as well as other functional cellular bioassays. We focused on processes linked with endocrine disruption, tumor promotion and/or regulation of transcription factors controlling metabolism of both endogenous compounds and xenobiotics. The tested LC-PCBs were found to be mostly efficient anti-androgenic (within nanomolar - micromolar range) and estrogenic (at micromolar concentrations) compounds, as well as inhibitors of gap junctional intercellular communication (GJIC) at micromolar concentrations. PCB 8, 28 and 31 were found to partially inhibit the aryl hydrocarbon receptor (AhR)-mediated activity. The tested LC-PCBs were also partial constitutive androstane receptor (CAR) and pregnane X receptor (PXR) agonists, with PCB 4, 8 and 18 being the most active compounds. They were inactive towards other nuclear receptors, such as vitamin D receptor, thyroid receptor α, glucocorticoid receptor or peroxisome proliferator-activated receptor γ. We found that only PCB 8 contributed to generation of oxidative stress, while all tested LC-PCBs induced arachidonic acid release (albeit without further modulations of arachidonic acid metabolism) in human lung epithelial cells. Importantly, estrogenic effects of hydroxylated (OH-PCB) metabolites of LC-PCBs (4-OH-PCB 8, 4-OH-PCB 11 and 4'-OH-PCB 18) were higher than those of the parent PCBs, while their other toxic effects were only slightly altered or suppressed. This suggested that metabolism may alter toxicity profiles of LC-PCBs in a receptor-specific manner. In summary, anti-androgenic and estrogenic activities, acute inhibition of GJIC and suppression of the AhR-mediated activity were found to be the most relevant modes of action of airborne LC-PCBs, although they partially affected also additional cellular targets.
- Klíčová slova
- Airborne polychlorinated biphenyls, Endocrine disruption, HydroxyLated PCBs, Metabolism of xenobiotics, Tumor promotion,
- MeSH
- buněčné linie MeSH
- endokrinní disruptory metabolismus toxicita MeSH
- epitelové buňky účinky léků MeSH
- hydroxylace MeSH
- konstitutivní androstanový receptor MeSH
- látky znečišťující vzduch toxicita MeSH
- lidé MeSH
- nádory metabolismus MeSH
- polychlorované bifenyly metabolismus toxicita MeSH
- pregnanový X receptor MeSH
- receptory cytoplazmatické a nukleární metabolismus MeSH
- signální transdukce účinky léků MeSH
- steroidní receptory metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- endokrinní disruptory MeSH
- konstitutivní androstanový receptor MeSH
- látky znečišťující vzduch MeSH
- polychlorované bifenyly MeSH
- pregnanový X receptor MeSH
- receptory cytoplazmatické a nukleární MeSH
- steroidní receptory MeSH
In this work, we studied model stratum corneum lipid mixtures composed of the hydroxylated skin ceramides N-lignoceroyl 6-hydroxysphingosine (Cer[NH]) and α-hydroxylignoceroyl phytosphingosine (Cer[AP]). Two model skin lipid mixtures of the composition Cer[NH] or Cer[AP], N-lignoceroyl sphingosine (Cer[NS]), lignoceric acid (C24:0) and cholesterol in a 0.5:0.5:1:1 molar ratio were compared. Model membranes were investigated by differential scanning calorimetry and 2H solid-state NMR spectroscopy at temperatures from 25 °C to 80 °C. Each component of the model mixture was specifically deuterated for selective detection by 2H NMR. Thus, the exact phase composition of the mixture at varying temperatures could be quantified. Moreover, using X-ray powder diffraction we investigated the lamellar phase formation. From the solid-state NMR and DSC studies, we found that both hydroxylated Cer[NH] and Cer[AP] exhibit a similar phase behavior. At physiological skin temperature of 32 °C, the lipids form a crystalline (orthorhombic) phase. With increasing temperature, most of the lipids become fluid and form a liquid-crystalline phase, which converts to the isotropic phase at higher temperatures (65-80 °C). Interestingly, lignoceric acid in the Cer[NH]-containing mixture has a tendency to form two types of fluid phases at 65 °C. This tendency was also observed in Cer[AP]-containing membranes at 80 °C. While Cer[AP]-containing lipid models formed a short periodicity phase featuring a repeat spacing of d = 5.4 nm, in the Cer[NH]-based model skin lipid membranes, the formation of unusual long periodicity phase with a repeat spacing of d = 10.7 nm was observed.
- Klíčová slova
- Hydroxylated skin ceramides, Lipid packing, Model membranes, Order parameter, Thermotropic phase behavior,
- MeSH
- biologické modely MeSH
- ceramidy chemie metabolismus MeSH
- cholesterol chemie MeSH
- deuterium chemie MeSH
- hydroxylace fyziologie MeSH
- kůže chemie metabolismus MeSH
- lidé MeSH
- lipidové dvojvrstvy chemie metabolismus MeSH
- magnetická rezonanční spektroskopie metody MeSH
- permeabilita buněčné membrány MeSH
- prášková difrakce metody MeSH
- rentgenové záření MeSH
- teplota kůže fyziologie MeSH
- teplota MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ceramidy MeSH
- cholesterol MeSH
- deuterium MeSH
- lipidové dvojvrstvy MeSH
The objective of this study was to elucidate the pharmacokinetics and metabolite formation of newly developed non-selective AChE/BChE 7-MEOTA-donepezil-like inhibitors for potential therapeutic use in Alzheimer's disease (AD) patients. The chemical structures of metabolites were defined during incubation with human liver microsomes, and subsequently, the metabolization was verified in in vivo study. In vitro metabolic profiling revealed the formation of nine major metabolites in the case of PC-37 and eight metabolites of PC-48. Hydroxylation and the enzymatic hydrolysis of bonds close to the piperazine ring appeared to be the principal metabolic pathways in vitro. Of these metabolites, M1-M7 of PC-37 and M1-M6 of PC-48 were confirmed under in vivo conditions. Pilot pharmacokinetic experiments in rats were focused on the absorption, distribution and elimination of these compounds. Absorption after i.m. application was relatively fast; the bioavailability expressed as AUCtotal was 28179 ± 4691 min.ng/mL for PC-37 and 23374 ± 4045 min.ng/mL for PC-48. Both compounds showed ability to target the central nervous system, with brain concentrations exceeding those in plasma. The maximal brain concentrations are approximately two times higher than the plasma concentrations. The relatively high brain concentrations persisted throughout the experiment until 24 hr after application. Elimination via the kidneys (urine) significantly exceeded elimination via the liver (bile). All these characteristics are crucial for new candidates intended for AD treatment. The principle metabolic pathways that were verified in the in vivo study do not show any evidence for formation of extremely toxic metabolites, but this needs to be confirmed by further studies.
- MeSH
- Alzheimerova nemoc farmakoterapie MeSH
- biologická dostupnost MeSH
- cholinesterasové inhibitory chemická syntéza metabolismus farmakokinetika terapeutické užití MeSH
- hydrolýza MeSH
- hydroxylace MeSH
- jaterní mikrozomy metabolismus MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- metabolické sítě a dráhy MeSH
- mozek účinky léků MeSH
- pilotní projekty MeSH
- piperaziny chemická syntéza metabolismus farmakokinetika terapeutické užití MeSH
- potkani Wistar MeSH
- takrin analogy a deriváty chemická syntéza metabolismus farmakokinetika terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 7-methoxy-N-(2-(4-(3-methylbenzyl)piperazine-1-yl)ethyl)-1,2,3,4-tetrahydroacridin-9-amine MeSH Prohlížeč
- cholinesterasové inhibitory MeSH
- N-(2-(4-(3-bromobenzyl)piperazine-1-yl)ethyl)-7-methoxy-1,2,3,4-tetrahydroacridin-9-amine MeSH Prohlížeč
- piperaziny MeSH
- takrin MeSH
Warfarin is a commonly used anticoagulant drug and is a derivate of coumarin. Cytochrome P450 2C9 (CYP2C9) plays the key role in transformation of coumarin and thus, influences determination of warfarin dosage. A number of factors including dietary compounds such as sesamin, caffeic acid and ferulic acids can regulate the activity of CYP2C9. The present study tested the hypothesis that sesamin, episesamin, caffeic acid and ferulic acid decreases the rate of warfarin 7-hydroxylation via inhibition of hepatic CYP2C9. The experiments were conducted on hepatic microsomes from human donors. It was demonstrated that the rate of 7-hydroxylation of warfarin was significantly decreased in the presence of sesamin in the range of concentrations from 5 to 500 nM, and was not affected by episesamin, caffeic acid and ferulic acid in the same range of concentrations. The kinetic analysis indicated non-competitive type of inhibition by sesamin with Ki = 202 ± 18 nM. In conclusion, the results of our in vitro study revealed that sesamin was able to inhibit formation of a major metabolite of warfarin, 7-hydroxywarfarin. The potentially negative consequences of the consumption of high amounts of sesamin-containing food or dietary supplements in warfarin-treated patients need to be further studied.
- Klíčová slova
- Cytochrome P450, Detoxification, Food-drug interactions, In vitro, S-7-hydroxywarfarin,
- MeSH
- antikoagulancia metabolismus MeSH
- dioxoly chemie farmakologie MeSH
- hydroxylace MeSH
- inhibiční koncentrace 50 MeSH
- jaterní mikrozomy metabolismus MeSH
- kinetika MeSH
- kyseliny kávové farmakologie MeSH
- kyseliny kumarové farmakologie MeSH
- lidé MeSH
- lignany chemie farmakologie MeSH
- potraviny MeSH
- potravní doplňky MeSH
- warfarin metabolismus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antikoagulancia MeSH
- caffeic acid MeSH Prohlížeč
- dioxoly MeSH
- ferulic acid MeSH Prohlížeč
- kyseliny kávové MeSH
- kyseliny kumarové MeSH
- lignany MeSH
- sesamin MeSH Prohlížeč
- warfarin MeSH
Amlodipine (AML) is available as a racemate, i.e., a mixture of R- and S-enantiomers. Its inhibitory potency towards nine cytochromes P450 (CYP) was studied to evaluate the drug-drug interactions between the enantiomers. Enzyme inhibition was evaluated using specific CYP substrates in human liver microsomes. With CYP3A, both enantiomers exhibited reversible and time-dependent inhibition. S-AML was a stronger reversible inhibitor of midazolam hydroxylation: the Ki values of S- and R-AML were 8.95 µM, 14.85 µM, respectively. Computational docking confirmed that the enantiomers interact differently with CYP3A: the binding free energy of S-AML in the active site was greater than that for R-AML (-7.6- vs. -6.7 kcal/mol). Conversely, R-AML exhibited more potent time-dependent inhibition of CYP3A activity (KI 8.22 µM, Kinact 0.065 min-1) than S-AML (KI 14.06 µM, Kinact 0.041 min-1). R-AML was also a significantly more potent inhibitor of CYP2C9 (Ki 12.11 µM/S-AML 21.45 µM) and CYP2C19 (Ki 5.97 µM/S-AML 7.22 μM. In conclusion, results indicate that clinical use of S-AML has an advantage not only because of greater pharmacological effect, but also because of fewer side effects and drug-drug interactions with cytochrome P450 substrates due to absence of R-AML.
- Klíčová slova
- amlodipine, cytochrome P450, drug–drug interactions, enantiomers, enzyme inhibition, stereoselectivity,
- MeSH
- amlodipin chemie farmakologie MeSH
- hydroxylace MeSH
- inhibitory cytochromu P450 CYP3A chemie farmakologie MeSH
- inhibitory cytochromu P450 chemie farmakologie MeSH
- jaterní mikrozomy metabolismus MeSH
- kinetika MeSH
- lékové interakce MeSH
- lidé MeSH
- midazolam metabolismus MeSH
- molekulární struktura MeSH
- simulace molekulového dockingu MeSH
- stereoizomerie MeSH
- systém (enzymů) cytochromů P-450 metabolismus MeSH
- termodynamika MeSH
- vazebná místa MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- amlodipin MeSH
- inhibitory cytochromu P450 CYP3A MeSH
- inhibitory cytochromu P450 MeSH
- midazolam MeSH
- systém (enzymů) cytochromů P-450 MeSH
Lysine hydroxylation of type I collagen telopeptides varies from tissue to tissue, and these distinct hydroxylation patterns modulate collagen cross-linking to generate a unique extracellular matrix. Abnormalities in these patterns contribute to pathologies that include osteogenesis imperfecta (OI), fibrosis, and cancer. Telopeptide procollagen modifications are carried out by lysyl hydroxylase 2 (LH2); however, little is known regarding how this enzyme regulates hydroxylation patterns. We identified an ER complex of resident chaperones that includes HSP47, FKBP65, and BiP regulating the activity of LH2. Our findings show that FKBP65 and HSP47 modulate the activity of LH2 to either favor or repress its activity. BiP was also identified as a member of the complex, playing a role in enhancing the formation of the complex. This newly identified ER chaperone complex contributes to our understanding of how LH2 regulates lysyl hydroxylation of type I collagen C-telopeptides to affect the quality of connective tissues. © 2017 American Society for Bone and Mineral Research.
- MeSH
- biologické modely MeSH
- buněčné linie MeSH
- chaperon endoplazmatického retikula BiP MeSH
- hmotnostní spektrometrie MeSH
- hydroxylace MeSH
- kolagen typu I metabolismus MeSH
- lidé MeSH
- lysin metabolismus MeSH
- lysinhydroxylasa metabolismus MeSH
- multiproteinové komplexy metabolismus MeSH
- mutace genetika MeSH
- myši MeSH
- peptidy metabolismus MeSH
- povrchová plasmonová rezonance MeSH
- prokolagen metabolismus MeSH
- proteiny tepelného šoku HSP47 metabolismus MeSH
- proteiny tepelného šoku metabolismus MeSH
- proteiny vázající takrolimus metabolismus MeSH
- stabilita enzymů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chaperon endoplazmatického retikula BiP MeSH
- collagen type I trimeric cross-linked peptide MeSH Prohlížeč
- FKBP10 protein, human MeSH Prohlížeč
- kolagen typu I MeSH
- lysin MeSH
- lysinhydroxylasa MeSH
- multiproteinové komplexy MeSH
- peptidy MeSH
- prokolagen MeSH
- proteiny tepelného šoku HSP47 MeSH
- proteiny tepelného šoku MeSH
- proteiny vázající takrolimus MeSH
- SERPINH1 protein, human MeSH Prohlížeč