Jana Sladkova

Charles University in Prague, Praha, Praha, Czech Republic

Are you Jana Sladkova?

Claim your profile

Publications (14)

  • Hana Kratochvílová · Marie Rodinová · Jana Sládková · [...] · Markéta Tesařová
    Article · Nov 2015
  • Source
    J Sládková · J Spáčilová · M Čapek · [...] · J Zeman
    [Show abstract] [Hide abstract] ABSTRACT: Mitochondrial morphology was studied in cultivated myoblasts obtained from patients with mitochondrial disorders, including CPEO, MELAS and TMEM70 deficiency. Mitochondrial networks and ultrastructure were visualized by fluorescence microscopy and transmission electron microscopy, respectively. A heterogeneous picture of abnormally sized and shaped mitochondria with fragmentation, shortening, and aberrant cristae, lower density of mitochondria and an increased number of "megamitochondria" were found in patient myoblasts. Morphometric Fiji analyses revealed different mitochondrial network properties in myoblasts from patients and controls. The small number of cultivated myoblasts required for semiautomatic morphometric image analysis makes this tool useful for estimating mitochondrial disturbances in patients with mitochondrial disorders.
    Full-text available · Article · Jul 2015 · Ultrastructural Pathology
  • [Show abstract] [Hide abstract] ABSTRACT: The most pathological effects of Huntington’s disease (HD) are focused on the central nervous system but numerous reports had described abnormalities in peripheral tissues. Mutant huntingtin (Htt) has been implicated in disruptions of multiple cellular processes, including mitochondrial functions whose impairment contributes to the pathogenesis of HD. The aim was to analyse mitochondrial bioenergetics in somatic and germ cells from HD patients and minipig boars transgenic (TgHD) for the N-terminal part of human mutated Htt. Material Cultivated fibroblasts, sperm and buccal epithelial cells (BEC) were collected after informed consent from 8 HD symptomatic patients (22–74 years) with 43–58 CAG triplet repeats and from TgHD and WT minipigs of F0 - F2 generations (12–60 months). Methods Respiratory chain complexes (RCC) activity and amount were analysed by spectrophotometric, imunoelectrophoretic and by dipstick immunocapture method (Mitosciences). Respiration was measured by polarography. Mitochondrial energy generating system (MEGS) capacity was characterised by oxidation rate of labelled substrates. Mitochondrial ultrastructure, network and reactive oxygen species (ROS) were visualised using fluorescent and electron microscopy. Results Swollen mitochondria, fragmented network, increased ROS level, decreased respiration and selectively decreased level of RCC I and IV were detected in HD patient´s and TgHD minipig fibroblasts in comparison with controls. Impaired mitochondrial respiration, reduced MEGS and decreased RCC II activity was found in sperm of TgHD boars and in one HD patient. Amount of RCC I and IV in BEC was decreased in all HD patients and in two from three asymptomatic TgHD minipigs compared to controls. Conclusion Tested cells could serve for noninvasive monitoring of mitochondrial impairment incurred in connexion with HD even in presymptomatic stages of disease. Supported TA01011466, ExAM-CZ.1.05./2.1.00/03.0124, PRVOUK-P24/LF1/3, PRVOUK-P26/LF1/4.
    Article · Sep 2014 · Journal of Neurology Neurosurgery & Psychiatry
  • Hana Hansikova · Jana Sladkova · Marie Rodinova · [...] · Anna Sediva
    Conference Paper · Aug 2014
  • Source
    A Sediva · H Hansikova · J Sladkova · [...] · P Szturz
    Full-text available · Article · Nov 2013 · Pediatric Rheumatology
  • Source
    J. Spacilova · K. Vesela · J. Sladkova · [...] · J. Zeman
    Full-text available · Conference Paper · Oct 2012
  • Source
    Full-text available · Article · Oct 2012 · Biochimica et Biophysica Acta (BBA) - Bioenergetics
  • Article · Sep 2012 · Mitochondrion
  • Source
    Dataset: Table S1
    [Show abstract] [Hide abstract] ABSTRACT: Protein identification summary. Table listing the identified proteins for each of the spots of interest and identification characteristics. In addition, fold changes of spot intensities between MPC and MTT cells from the preparative gels are listed. Fold changes listed here together with the protein IDs were used for Ingenuity Pathway Analysis. (XLSX)
    File available · Dataset · Jul 2012
  • Source
    [Show abstract] [Hide abstract] ABSTRACT: A glycolytic profile unifies a group of pheochromocytomas and paragangliomas (PHEOs/PGLs) with distinct underlying gene defects, including von Hippel-Lindau (VHL) and succinate dehydrogenase B (SDHB) mutations. Nevertheless, their tumor aggressiveness is distinct: PHEOs/PGLs metastasize rarely in VHL-, but frequently in SDHB-patients. To date, the molecular mechanisms causing the more aggressive phenotype in SDHB-PHEOs/PGLs remain largely unknown. Recently, however, an excellent model to study aggressive PHEOs (mouse tumor tissue (MTT) cells) has been developed from mouse PHEO cells (MPC). We employed this model for a proteomics based approach to identify changes characteristic for tumor aggressiveness, which we then explored in a homogeneous set of human SDHB- and VHL-PHEOs/PGLs. The increase of glucose transporter 1 in VHL, and of hexokinase 2 in VHL and SDHB, confirmed their glycolytic profile. In agreement with the cell model and in support of decoupling of glycolysis, the Krebs cycle and oxidative phosphorylation (OXPHOS), SDHB tumors showed increased lactate dehydrogenase levels. In SDHB-PGLs OXPHOS complex activity was increased at complex III and, as expected, decreased at complex II. Moreover, protein and mRNA expression of all tested OXPHOS-related genes were higher in SDHB- than in VHL-derived tumors. Although there was no direct evidence for increased reactive oxygen species production, elevated superoxide dismutase 2 expression may reflect elevated oxidative stress in SDHB-derived PHEOs/PGLs. For the first time, we show that despite dysfunction in complex II and evidence for a glycolytic phenotype, the Warburg effect does not seem to fully apply to SDHB-PHEOs/PGLs with respect to decreased OXPHOS. In addition, we present evidence for increased LDHA and SOD2 expression in SDHB-PHEOs/PGLs, proteins that have been proposed as promising therapeutic targets in other cancers. This study provides new insight into pathogenic mechanisms in aggressive human PHEOs/PGLs, which may lead to identifying new diagnostic and prognostic markers in the near future.
    Full-text available · Article · Jul 2012 · PLoS ONE
  • Source
    Dataset: Table S2
    [Show abstract] [Hide abstract] ABSTRACT: Peptide identification summary. Table listing the characteristics of detected peptides for each spot, including their sequences and database search specifics. (XLS)
    File available · Dataset · Jul 2012
  • L Zídková · J Krijt · J Sládková · [...] · T Adam
    [Show abstract] [Hide abstract] ABSTRACT: Succinylpurines accumulate in the body fluids of patients with adenylosuccinate lyase (ADSL) deficiency but their source in the cerebrospinal fluid remains obscure. Study based on the incorporation of 13C-stable isotope-labeled glycine into cultured oligodendroglia from ADSL-deficient patient and the measurement of labeled products by LC/MS/MS showed total intracellular concentrations of succinylpurines from 45 to 99μmol/l and so these results suggest that these cells can be the source of the compounds in vivo.
    Article · Oct 2010 · Molecular Genetics and Metabolism
  • Source
    Olga Brantova · Befekadu Asfaw · Jana Sladkova · [...] · Jiri Zeman
    [Show abstract] [Hide abstract] ABSTRACT: α-Mannosidosis is a lysosomal storage disorder caused by α-mannosidase deficiency. Clinical course of the disease ranges from severe infantile to milder juvenile type and includes mental retardation, skeletal deformities, coarse facies, hepatomegaly and hearing loss. The aim of the study was to analyse mitochondrial ultrastructure and function in cultivated fibroblasts from three patients with α-mannosidosis. All patients were homozygous for the c.2248C>T mutation in the MAN2B1 gene encoding lysosomal α-mannosidase. The mutation results in incorrect protein folding and severe decrease of α-mannosidase activity. The misfolded protein is retained by the control system of endoplasmic reticulum (ER). In analysed fibroblasts, we observed dilated ER, higher amount of aberrant mitochondria and reduced mitochondrial mass compared to controls. Respiratory chain complex IV, cytochrome c oxidase (COX), activity and the ratio between COX and citrate synthase (control enzyme) were significantly increased in comparison to controls (P < 0.05). Furthermore, the activity at least from one of other respiratory chain complexes was increased in each studied cell line. Mitochondrial membrane potential as well as reactive oxygen species production were comparable with controls. Based on our results, we hypothesize more profound effect of swelled and damaged mitochondria and ER dilatation on tissues with higher energy demand than fibroblasts have.
    Full-text available · Article · Apr 2009 · Biologia
  • Source
    Olga Brantová · Markéta Tesarová · Hana Hansíková · [...] · Jana Sládková
    [Show abstract] [Hide abstract] ABSTRACT: Mitochondrial disorders represent a heterogeneous group of multisystem diseases with extreme variability in clinical phenotype. The diagnosis of mitochondrial disorders relies heavily on extensive biochemical and molecular analyses combined with morphological studies including electron microscopy. Although muscle is the tissue of choice for electron microscopic studies, the authors investigated cultivated human skin fibroblasts (HSF) harboring 3 different pathologic mtDNA mutations: 3243A > G, 8344A > G, 8993T > G. They addressed to the possibility of whether mtDNA mutations influence mitochondrial morphology in HSF and if ultrastructural changes of mitochondria may be used for differential diagnostics of mitochondrial disorders caused by mtDNA mutations. Ultrastructural analysis of patients' HSF revealed a heterogeneous mixture of mainly abnormal, partially swelling mitochondria with unusual and sparse cristae. The most characteristic cristal abnormalities were heterogeneity in size and shapes or their absence. Typical filamentous and branched mitochondria with numerous cristae as appeared in control HSF were almost not observed. In all lines of cultured HSF with various mtDNA mutations, similar ultrastructural abnormalities and severely changed mitochondrial interior were found, although no alterations in function and amount of OXPHOS were detected by routinely used biochemical methods in two lines of cultured HSF. This highlights the importance of morphological analysis, even in cultured fibroblasts, in diagnostics of mitochondrial disorders.
    Full-text available · Article · Jul 2006 · Ultrastructural Pathology

Publication Stats

25 Citations


  • 2013-2014
    • Charles University in Prague
      Praha, Praha, Czech Republic