Miroslav Strnad

Palacký University of Olomouc, Olmütz, Olomoucký, Czech Republic

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Publications (123)364.12 Total impact

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    ABSTRACT: Clusterin, a heterodimeric glycoprotein, is thought to be involved in many cellular functions, including cell–cell interaction, cell survival and apoptosis. In the brain, post-mortem analysis has found increased clusterin associated with the pathology of many other neurodegenerative diseases (ND) such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), Alzheimer's disease (AD) and multiple system atrophy (MSA). In vivo cerebrospinal fluid (CSF) levels of clusterin in ND diseases may reflect differences in the pathology and thus aid in the differential diagnosis.
    No preview · Article · Feb 2016
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    Preview · Article · Oct 2015
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    ABSTRACT: Here we describe the leishmanicidal activities of a library of 2,6,9-trisubstituted purines that were screened for interaction with Cdc2-related protein kinase 3 (CRK3) and subsequently for activity against parasitic Leishmania species. The most active compound inhibited recombinant CRK3 with an IC50 value of 162nM and was active against Leishmania major and Leishmania donovani at low micromolar concentrations in vitro. Its mode of binding to CRK3 was investigated by molecular docking using a homology model. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Apr 2015 · Bioorganic & medicinal chemistry letters
  • S. Malik · O. Bíba · J. Grúz · R.R.J. Arroo · M. Strnad
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    ABSTRACT: The genus Linum includes more than 230 globally distributed species, which have attracted great interest as they grow rapidly and are already sources of commercially important products, e.g. flax and linseed oil. Furthermore, they contain lignans such as podophyllotoxin (PTOX), deoxypodophyllotoxin (a precursor of both PTOX and 6-methoxypodophyllotoxin, the latter via β-peltatin, and β-peltatin-A-methyl ether) and various derivatives. Lignans are natural compounds derived from two 8,8′-linked C6C3 (propylbenzene) units. PTOX is an aryltetralin-lignan with strong cytotoxic and antiviral activities. Thus, it is used as a starting material for producing various semisynthetic derivatives that are widely used in chemotherapy, such as etoposide, teniposide and etopophos. It is currently produced largely from Podophyllum hexandrum and P. peltatum, slow-growing endangered species of the Berberidaceae. Hence, the possibility of producing it from Linum, especially members of section Syllinum under either in vitro or ex vitro conditions is highly attractive. This review summarizes related research, focusing on in vitro production of aryltetralin lignans from various Linum species and possible biotechnological strategies to improve their production. The key pathways, enzymes and genes involved are highlighted and future challenges that must be met to allow viable, large-scale production of this anticancer drug lead are discussed.
    No preview · Article · Dec 2014 · Phytochemistry Reviews
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    ABSTRACT: Background: Parkinson's disease (PD), PD with dementia (PDD) and Lewy body dementia (DLB) are synucleinopathies. PDD and DLB are sometimes considered a transition between PD and Alzheimer dementia (AD). Finding in vivo markers or their combination could help in the differential diagnosis of these neurodegenerative (ND) diseases. Objective: The aim of this study was to assess cerebrospinal fluid (CSF) levels of tau protein, betaamyloid(1-42) and clusterin and to compare these levels among patients with probable PD, PDD, DLB and AD. Methods: CSF levels of ND markers were assessed in 96 patients (27 patients with PD, 14 with PDD, 14 with DLB, 17 with AD and 24 subjects as a control group). Results: In all of the groups of patients, beta-amyloid(1-42) levels were decreasing in the order PD > PDD > DLB > AD, whereas tau protein and the tau protein/beta-amyloid(1-42) index were increasing in the same order (PD < PDD < AD), except for DLB. In paired group comparisons, higher levels of clusterin in PD patients (p = 0.005) and PDD patients (p = 0.052) compared to the CG were found. Conclusion: The results of the present study support the role of clusterin in PD pathogenesis. The decreasing CSF beta-amyloid(1-42) levels in the order PDD, DLB and AD may relate to the increasing presence of AD pathology in these disorders.
    No preview · Article · Jun 2014 · Journal of the Neurological Sciences
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    Full-text · Dataset · Nov 2013
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    Full-text · Dataset · Oct 2013
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    ABSTRACT: Endogenous gibberellins and brassinosteroids were quantified in 24 axenic microalgae strains from the Chlorophyceae, Trebouxiophyceae, Ulvophyceae and Charophyceae microalgae strains after 4 days in culture. This is the first report of endogenous gibberellins being successfully detected in microalgae. Between 18 and 20 gibberellins were quantified in all strains with concentrations ranging from 342.7 pg mg(-1) DW in Raphidocelis subcapitata MACC 317-4746.1 pg mg(-)(1) DW in Scotiellopsis terrestris MACC 44. Slower growing strains (S. terrestris MACC 44, Gyoerffyana humicola MACC 334, Nautococcus mamillatus MACC 716 and Chlorococcum ellipsoideum MACC 712) exhibited the highest gibberellin contents while lowest levels of gibberellins were found in faster growing strains (R. subcapitata MACC 317 and Coelastrum excentrica MACC 504). In all strains, the active gibberellin detected in the highest concentration was GA6, the predominant intermediates were GA15 and GA53 and the main biosynthetic end products were GA13 and GA51. Gibberellin profiles were similar in all strains except for the presence/absence of GA12 and GA12ald. To date this is the second report of endogenous brassinosteroids in microalgae. Brassinosteroids were detected in all 24 strains with concentrations ranging from 117.3 pg mg(-)(1) DW in R. subcapitata MACC 317-977.8 pg mg(-)(1) DW in Klebsormidium flaccidum MACC 692. Two brassinosteroids, brassinolide and castasterone were determined in all the strains. Generally, brassinolide occurred in higher concentrations than castasterone.
    Full-text · Article · Jun 2013 · Plant Physiology and Biochemistry
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    ABSTRACT: Verticillium longisporum is a vascular pathogen that infects the Brassicaceae host plants Arabidopsis thaliana and Brassica napus. The soil-borne fungus enters the plant via the roots and colonizes the xylem of roots, stems and leaves. During late stages of infections, Verticillium spreads into senescing tissue and switches from biotrophic to a necrotrophic life style. Typical symptoms of Verticillium longisporum-induced disease are stunted growth and leaf chloroses. Expression analyses of the senescence marker genes SENESCENCE ASSOCIATED GENE12, SENESCENCE ASSOCIATED GENE13 and WRKY53 revealed that the observed chloroses are a consequence of premature senescence triggered by Verticillium infection. Our analyses show that concomitant with the development of chloroses levels of trans-zeatin decrease in infected plants. Potentially, induction of cytokinin oxidase expression by Verticillium infection contributes to the observed decreases in cytokinin levels. Stabilisation of Arabidopsis cytokinin levels by both pharmacological and genetic approaches inhibits Verticillium proliferation and coincides with reduced disease symptom development. In summary, our results indicate that Verticillium triggers premature plant senescence for efficient host plant colonization.
    No preview · Article · Apr 2013 · Molecular Plant-Microbe Interactions
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    ABSTRACT: Metastases destroy the function of infested organs and are the main reason of cancer-related mortality. Heteronemin, a natural product derived from a marine sponge, was tested in vitro regarding its properties to prevent tumour cell intravasation through the lymph-endothelial barrier. In three-dimensional (3D) cell cultures consisting of MCF-7 breast cancer cell spheroids that were placed on lymph-endothelial cell (LEC) monolayers, tumour cell spheroids induce "circular chemorepellent-induced defects" (CCIDs) in the LEC monolayer; 12(S)-Hydroxyeicosatetraenoic acid (12(S)-HETE) and NF-κB activity are major factors inducing CCIDs, which are entry gates for tumour emboli intravasating the vasculature. This 3D co-culture is a validated model for the investigation of intravasation mechanisms and of drugs preventing CCID formation and hence lymph node metastasis. Furthermore, Western blot analyses, NF-κB reporter, EROD, SELE, 12(S)-HETE, and adhesion assays were performed to investigate the properties of heteronemin. Five micromolar heteronemin inhibited the directional movement of LECs and, therefore, the formation of CCIDs, which were induced by MCF-7 spheroids. Furthermore, heteronemin reduced the adhesion of MCF-7 cells to LECs and suppressed 12(S)-HETE-induced expression of the EMT marker paxillin, which is a regulator of directional cell migration. The activity of CYP1A1, which contributed to CCID formation, was also inhibited by heteronemin. Hence, heteronemin inhibits important mechanisms contributing to tumour intravasation in vitro and should be tested in vivo.
    Full-text · Article · Mar 2013 · Archives of Toxicology
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    ABSTRACT: Health beneficial effects of xanthohumol have been reported, and basic research provided evidence for anti-cancer effects. Furthermore, xanthohumol was shown to inhibit the migration of endothelial cells. Therefore, this study investigated the anti-metastatic potential of xanthohumol. MCF-7 breast cancer spheroids which are placed on lymphendothelial cells (LECs) induce "circular chemorepellent-induced defects" (CCIDs) in the LEC monolayer resembling gates for intravasating tumour bulks at an early step of lymph node colonisation. NF-κB reporter-, EROD-, SELE-, 12(S)-HETE- and adhesion assays were performed to investigate the anti-metastatic properties of xanthohumol. Western blot analyses were used to elucidate the mechanisms inhibiting CCID formation. Xanthohumol inhibited the activity of CYP, SELE and NF-kB and consequently, the formation of CCIDs at low micromolar concentrations. More specifically, xanthohumol affected ICAM-1 expression and adherence of MCF-7 cells to LECs, which is a prerequisite for CCID formation. Furthermore, markers of epithelial-to-mesenchymal transition (EMT) and of cell mobility such as paxillin, MCL2 and S100A4 were suppressed by xanthohumol. Xanthohumol attenuated tumour cell-mediated defects at the lymphendothelial barrier and inhibited EMT-like effects thereby providing a mechanistic explanation for the anti-intravasative/anti-metastatic properties of xanthohumol.
    Full-text · Article · Mar 2013 · Archives of Toxicology
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    ABSTRACT: Upward leaf movement, called hyponastic growth, is employed by plants to cope with adverse environmental conditions. Ethylene is a key regulator of this process and, in Arabidopsis thaliana, hyponasty is induced by this phytohormone via promotion of epidermal cell expansion in a proximal zone of the abaxial side of the petiole. ROTUNDIFOLIA3/CYP90C1 encodes an enzyme which was shown to catalyse C-23 hydroxylation of several brassinosteroids (BRs) – phytohormones involved in, for example, organ growth, cell expansion, cell division, and responses to abiotic and biotic stresses. This study tested the interaction between ethylene and BRs in regulating hyponastic growth. A mutant isolated in a forward genetic screen, with reduced hyponastic response to ethylene treatment, was allelic to rot3. The cause of the reduced hyponastic growth in this mutant was examined by studying ethylene–BR interaction during local cell expansion, pharmacological inhibition of BR synthesis and ethylene effects on transcription of BR-related genes. This work demonstrates that rot3 mutants are impaired in local cell expansion driving hyponasty. Moreover, the inhibition of BR biosynthesis reduces ethylene-induced hyponastic growth and ethylene increases sensitivity to BR in promoting cell elongation in Arabidopsis hypocotyls. Together, the results show that ROT3 modulates ethylene-induced petiole movement and that this function is likely BR related.
    Full-text · Article · Dec 2012 · Journal of Experimental Botany
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    ABSTRACT: In Pinus radiata D. Don, the transition from the juvenile to the mature phase is characterized by a reduction in the tree's organogenic potential, which is usually reverted in breeding programs by reinvigoration procedures to enable vegetative propagation. In this work we have determined the best culture conditions for in vitro reinvigoration of radiata pine buds, tested different cytokinin types (N(6) -benzyladenine, meta-topolin and trans-zeatin) and concentrations (25 and 50 μM), and studied the effect of culture conditions on endogenous cytokinin and indole-3-acetic acid levels at different stages of the organogenic process. To this end, the levels of 43 cytokinins and indole-3-acetic acid were determined in Pinus radiata buds before and during the reinvigoration process. When N(6) -benzyladenine or meta-topolin was applied to the induction medium, we did not observe any significant increase or decrease in endogenous isoprenoid cytokinin content. We also report for the first time the presence of O-glucosides in non-treated Pinus radiata explants from the field and remark the importance of O-glucosides as storage forms.
    No preview · Article · Oct 2012 · Physiologia Plantarum
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    ABSTRACT: Jasmonates (JAs) are ubiquitously occurring signaling compounds in plants formed in response to biotic and abiotic stress as well as in development. (+)-7-iso-jasmonoyl isoleucine, the bioactive JA, is involved in most JA-dependent processes mediated by the F-box protein COI1 in a proteasome-dependent manner. However, there is an increasing number of examples, where the precursor of JA biosynthesis, cis-(+)-12-oxophytodienoic acid (OPDA) is active in a JA/COI1-independent manner. Here, we discuss those OPDA-dependent processes, thereby giving emphasis on tomato embryo development. Recent data on seed coat-generated OPDA and its role in embryo development is discussed based on biochemical and genetic evidences.
    Full-text · Article · Oct 2012 · Plant signaling & behavior
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    ABSTRACT: Caulogenesis in mature stone pine (Pinus pinea L.) cotyledons is promoted, to varying degrees depending on genotype, by exogenous application of the cytokinin (CK) benzyladenine (BA). In the present study, endogenous CK profiles of cotyledons from open-pollinated plants and two families of stone pine with widely differing organogenic capacities were monitored during caulogenesis and linked to previously characterized BA uptake and induction phases. Changes in levels of free bases, ribosides, ribotides and glucosides of both isoprenoid and aromatic CKs were followed. Before BA application, the pool of endogenous CKs in all sets of cotyledons was dominated by isoprenoid ribotides, but 1h after BA exposure, aromatic CKs (mainly active free bases and ribosides of topolins) accounted for more than 90% of the pool. BA N-glucosides were also observed, levels of which (and topolins) rose from 2d until the end of the (six-day) culture period. The CK profiles of the two selected pine families also differed, although the general trends were similar. During the first 6h, levels of BA and meta-topolin were highest in cotyledons from the family with the strongest caulogenic responses, while levels of ribotides and aromatic glucosides were highest in cotyledons from the other family.
    No preview · Article · Sep 2012 · Journal of Plant Physiology
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    ABSTRACT: Polyphenol oxidases (PPOs) are copper-binding enzymes of the plant secondary metabolism that oxidize polyphenols to quinones. Although PPOs are nearly ubiquitous in seed plants, knowledge on their evolution and function in other plant groups is missing. This study reports on the PPO gene family in the moss Physcomitrella patens (Hedw.) B.S.G. asan example for an early divergent plant. The P. patens PPO multigene family comprises 13 paralogues. Phylogenetic analyses suggest that plant PPOs evolved with the colonization of land and that PPO duplications within the monophyletic P. patens paralogue clade occurred after the separation of the moss and seed plant lineages. PPO functionality was demonstrated for recombinant PPO6. P. patens was analysed for phenolic compounds and six substances were detected intracellularly by LC-MS analysis: 4-hydroxybenzoic acid, p-cumaric acid, protocatechuic acid, salicylic acid, caffeic acid, and an ester of caffeic acid. Targeted PPO1 knockout (d|ppo1) plants were generated and plants lacking PPO1 exhibited only ~30% of the wild-type PPO activity in the culture medium, thus suggesting extracellular localization of PPO1, which is in contrast to the mostly plastidic PPO localization in seed plants. Further, d|ppo1 lines formed significantly more gametophores with a reduced areal plant size, which could be related to an increase of endogenously produced cytokinins and indicates an impact of PPO1 on plant development. d|ppo1 plants were less tolerant towards applied 4-methylcatechol compared to the wild type, which suggests a role of extracellular PPO1 in establishing appropriate conditions by the removal of inhibitory extracellular phenolic compounds.
    Full-text · Article · Aug 2012 · Journal of Experimental Botany
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    ABSTRACT: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand with selective antitumor activity. However, many primary tumors are TRAIL resistant. Previous studies reported that roscovitine, a cyclin-dependent kinase inhibitor, sensitized various solid cancer cells to TRAIL. We show that roscovitine and TRAIL demonstrate synergistic cytotoxicity in hematologic malignant cell lines and primary cells. Pretreatment of TRAIL-resistant leukemia cells with roscovitine induced enhanced cleavage of death-inducing signaling complex-bound proximal caspases after exposure to TRAIL. We observed increased levels of both pro- and antiapoptotic BCL-2 proteins at the mitochondria following exposure to roscovitine. These results suggest that roscovitine induces priming of cancer cells for death by binding antiapoptotic BCL-2 proteins to proapoptotic BH3-only proteins at the mitochondria, thereby decreasing the threshold for diverse proapoptotic stimuli. We propose that the mitochondrial priming and enhanced processing of apical caspases represent major molecular mechanisms of roscovitine-induced sensitization to TRAIL in leukemia/lymphoma cells.
    Full-text · Article · Jul 2012 · Leukemia & lymphoma
  • Claus Wasternack · Susanne Forner · Miroslav Strnad · Bettina Hause
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    ABSTRACT: Jasmonates are ubiquitously occurring lipid-derived signaling compounds active in plant development and plant responses to biotic and abiotic stresses. Upon environmental stimuli jasmonates are formed and accumulate transiently. During flower and seed development, jasmonic acid (JA) and a remarkable number of different metabolites accumulate organ- and tissue specifically. The accumulation is accompanied with expression of jasmonate-inducible genes. Among these genes there are defense genes and developmentally regulated genes. The profile of jasmonate compounds in flowers and seeds covers active signaling molecules such as JA, its precursor 12-oxophytodienoic acid (OPDA) and amino acid conjugates such as JA-Ile, but also inactive signaling molecules occur such as 12-hydroxy-JA and its sulfated derivative. These latter compounds can occur at several orders of magnitude higher level than JA. Metabolic conversion of JA and JA-Ile to hydroxylated compounds seems to inactivate JA signaling, but also specific functions of jasmonates in flower and seed development were detected. In tomato OPDA is involved in embryo development. Occurrence of jasmonates, expression of JA-inducible genes and JA-dependent processes in flower and seed development will be discussed.
    No preview · Article · Jun 2012 · Biochimie
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    ABSTRACT: Receptor-mediated endocytosis is an integral part of signal transduction as it mediates signal attenuation and provides spatial and temporal dimensions to signaling events. One of the best-studied leucine-rich repeat receptor-like kinases in plants, BRASSINOSTEROID INSENSITIVE 1 (BRI1), perceives its ligand, the brassinosteroid (BR) hormone, at the cell surface and is constitutively endocytosed. However, the importance of endocytosis for BR signaling remains unclear. Here we developed a bioactive, fluorescent BR analog, Alexa Fluor 647-castasterone (AFCS), and visualized the endocytosis of BRI1-AFCS complexes in living Arabidopsis thaliana cells. Impairment of endocytosis dependent on clathrin and the guanine nucleotide exchange factor for ARF GTPases (ARF-GEF) GNOM enhanced BR signaling by retaining active BRI1-ligand complexes at the plasma membrane. Increasing the trans-Golgi network/early endosome pool of BRI1-BR complexes did not affect BR signaling. Our findings provide what is to our knowledge the first visualization of receptor-ligand complexes in plants and reveal clathrin- and ARF-GEF-dependent endocytic regulation of BR signaling from the plasma membrane.
    Full-text · Article · May 2012 · Nature Chemical Biology
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    ABSTRACT: UPLC–ESI–MS/MS method was developed for the quantitative and qualitative analysis of 26 phenolic compounds in plant material, including 15 isoflavonoids (daidzein, genistein, isoformononetin, formononetin, prunetin, biochanin A, daidzin, genistin, ononin, sissotrin, osajin, pomiferin), 5 flavones (apigenin, kaempferol, quercetin, quercetin-3-glucoside, rutin), 4 flavanones (hesperetin, naringenin, naringenin-7-glucoside, naringin), a coumestan (coumestrol) and a coumarine (scopoletin). The analytes were detected in a multiple reaction monitoring mode and quantified using internal standards [13C3]daidzin, [2H6]naringenin and [2H4]genistein. Limits of detection were in the range 0.001–10 pmol injection−1. The precision of the method (relative standard deviation) ranged from 2.6 to 15.1% and the accuracy was –22.1 to 16.6%. Application of the method was demonstrated by the analysis of mung bean (Vigna radiata) sprout extract, in which 14 of the 26 analytes were detected and quantified.
    No preview · Article · May 2012 · Journal of Food Composition and Analysis

Publication Stats

5k Citations
364.12 Total Impact Points

Institutions

  • 1996-2015
    • Palacký University of Olomouc
      • • Department of Cell Biology and Genetics
      • • Laboratory of Growth Regulators
      • • Faculty of Science
      • • Department of Biophysics
      • • Laboratory of Molecular Pathology I
      Olmütz, Olomoucký, Czech Republic
  • 1996-2007
    • Academy of Sciences of the Czech Republic
      • • Isotope Laboratory
      • • Institute of Experimental Botany
      Praha, Praha, Czech Republic
  • 1997-2004
    • Institute of Experimental Botany AS CR
      Praha, Praha, Czech Republic
  • 1995-2002
    • University of Antwerp
      • Departement Biologie
      Antwerpen, Flanders, Belgium
  • 1999-2001
    • University of Tuebingen
      • Center for Plant Molecular Biology
      Tübingen, Baden-Württemberg, Germany