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3 results on '"Ingrid H. Hof"'

1. The Mitochondrial Epigenome: An Unexplored Avenue to Explain Unexplained Myopathies?

Author

Archibold Mposhi, Lin Liang, Kevin P. Mennega, Dilemin Yildiz, Crista Kampert, Ingrid H. Hof, Pytrick G. Jellema, Tom J. de Koning, Klaas Nico Faber, Marcel H. J. Ruiters, Klary E. Niezen-Koning, and Marianne G. Rots

Subjects
mitochondrial epigenome, myopathies, mitochondrial DNA methylation, cytochrome B, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Mutations in either mitochondrial DNA (mtDNA) or nuclear genes that encode mitochondrial proteins may lead to dysfunctional mitochondria, giving rise to mitochondrial diseases. Some mitochondrial myopathies, however, present without a known underlying cause. Interestingly, methylation of mtDNA has been associated with various clinical pathologies. The present study set out to assess whether mtDNA methylation could explain impaired mitochondrial function in patients diagnosed with myopathy without known underlying genetic mutations. Enhanced mtDNA methylation was indicated by pyrosequencing for muscle biopsies of 14 myopathy patients compared to four healthy controls, at selected cytosines in the Cytochrome B (CYTB) gene, but not within the displacement loop (D-loop) region. The mtDNA methylation patterns of the four healthy muscle biopsies were highly consistent and showed intriguing tissue-specific differences at particular cytosines with control skin fibroblasts cultured in vitro. Within individual myopathy patients, the overall mtDNA methylation pattern correlated well between muscle and skin fibroblasts. Despite this correlation, a pilot analysis of four myopathy and five healthy fibroblast samples did not reveal a disease-associated difference in mtDNA methylation. We did, however, detect increased expression of solute carrier family 25A26 (SLC25A26), encoding the importer of S-adenosylmethionine, together with enhanced mtDNA copy numbers in myopathy fibroblasts compared to healthy controls. To confirm that pyrosequencing indeed reflected DNA methylation and not bisulfite accessibility, mass spectrometry was employed. Although no myopathy-related differences in total amount of methylated cytosines were detected at this stage, a significant contribution of contaminating nuclear DNA (nDNA) was revealed, and steps to improve enrichment for mtDNA are reported. In conclusion, in this explorative study we show that analyzing the mitochondrial genome beyond its sequence opens novel avenues to identify potential molecular biomarkers assisting in the diagnosis of unexplained myopathies.

Published
2022
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2. Dopaminergic and serotonergic alterations in plasma in three groups of dystonia patients

Author

Martijn van Faassen, Marina A. J. Tijssen, Ingrid H. Hof, Tom J. de Koning, Anouk Kuiper, Ido P. Kema, Elze R. Timmers, Marenka Smit, K. E. Niezen-Koning, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Movement Disorder (MD), and Center for Liver, Digestive and Metabolic Diseases (CLDM)

Subjects
Adult, Male, medicine.medical_specialty, Levodopa, Serotonin, Adolescent, Dopamine, Motor Activity, Serotonergic, Young Adult, Internal medicine, otorhinolaryngologic diseases, Medicine, Humans, Cervical dystonia, Child, Torticollis, Aged, Dystonia, Aged, 80 and over, business.industry, Dopaminergic, Middle Aged, medicine.disease, nervous system diseases, Endocrinology, Monoamine neurotransmitter, Neurology, Dystonic Disorders, Case-Control Studies, Female, Neurology (clinical), Geriatrics and Gerontology, business, medicine.drug
Abstract

INTRODUCTION: In dystonia, dopaminergic alterations are considered to be responsible for the motor symptoms. Recent attention for the highly prevalent non-motor symptoms suggest also a role for serotonin in the pathophysiology. In this study we investigated the dopaminergic, serotonergic and noradrenergic metabolism in blood samples of dystonia patients and its relation with (non-)motor manifestations.METHODS: Concentrations of metabolites of dopaminergic, serotonergic and noradrenergic pathways were measured in platelet-rich plasma in 41 myoclonus-dystonia (M-D), 25 dopa-responsive dystonia (DRD), 50 cervical dystonia (CD) patients and 55 healthy individuals. (Non-)motor symptoms were assessed using validated instruments, and correlated with concentrations of metabolites.RESULTS: A significantly higher concentration of 3-methoxytyramine (0.03 vs. 0.02 nmol/L, p < 0.01), a metabolite of dopamine, and a reduced concentration of tryptophan (50 vs. 53 μmol/L, p = 0.03), the precursor of serotonin was found in dystonia patients compared to controls. The dopamine/levodopa ratio was higher in CD patients compared to other dystonia groups (p < 0.01). Surprisingly, relatively high concentrations of levodopa were found in the untreated DRD patients. Low concentrations of levodopa were associated with severity of dystonia (rs = -0.3, p < 0.01), depression (rs = -0.3, p < 0.01) and fatigue (rs = -0.2, p = 0.04).CONCLUSION: This study shows alterations in the dopaminergic and serotonergic metabolism of patients with dystonia, with dystonia subtype specific changes. Low concentrations of levodopa, but not of serotonergic metabolites, were associated with both motor and non-motor symptoms. Further insight into the dopaminergic and serotonergic systems in dystonia with a special attention to the kinetics of enzymes involved in these pathways, might lead to better treatment options.

Published
2021

3. Comparison of five incubation systems for rat liver slices using functional and viability parameters

Author

K. Groen, Henk J. Koster, Ingrid H. Hof, A.A.J.J.L. Rutten, K. van Twillert, G.M.M. (Geny) Groothuis, R. de Kanter, Peter Olinga, W.R. Leeman, Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding, Biopharmaceuticals, Discovery, Design and Delivery (BDDD), and Groningen Institute for Organ Transplantation (GIOT)

Subjects
Male, Cell viability, HEPATOCYTES, Animal tissue, law.invention, law, DYNAMIC ORGAN-CULTURE, Testosterone, Energy charge, Incubation, INDUCTION, Culture medium, Liver slice, Preservation, Biochemistry, Liver, Liver microsome metabolism, HEPATOTOXICITY, TOXICOLOGY, Biology, METABOLISM, Organ culture, Incubation period, Xenobiotics, Incubation time, Erlenmeyer flask, Incubation system, Organ Culture Techniques, Animals, Animalia, MTT assay, Viability assay, ENZYME-ACTIVITIES, Rats, Wistar, CUT TISSUE-SLICES, Pharmacology, Drug metabolism, Chromatography, L-Lactate Dehydrogenase, viability, Rat liver slices, CYTOCHROME-P450, Lidocaine, Phenazone, Nonhuman, Rats, ANTIPYRINE, Potassium, Vaibility, Energy Metabolism, Controlled study
Abstract

Precision-cut liver slices are presently used for various research objects, e.g. to study metabolism, transport, and toxicity of xenobiotics. Various incubation systems are presently employed, but a systematic comparison between these incubation systems with respect to preservation of slice function has not been performed yet. Therefore, we started a comparative study to evaluate five of these systems: the shaken flask (an Erlenmeyer in a shaking water bath), the stirred-well (24-well culture plate equipped with grids and magnetic stirrers), rocker platform (6-well culture plate with Netwell insert rocked on a platform), the roller system (dynamic organ culture rolled on an insert in a glass vial), and the 6-well shaker (6-well culture plate in a shaking water bath). The liver slices were incubated in these incubation systems for 0.5, 1.5, and 24.5 h and subsequently subjected to viability and metabolic function tests. The viability of the incubated liver slices was evaluated by: potassium content, MTT assay, energy charge, histomorphology, and LDH leakage. Their metabolic functions were studied by determination of the metabolism of lidocaine, testosterone, and antipyrine. Up to 1.5 h of incubation all five incubation systems gave similar results with respect to viability and metabolic function of the liver slices. However, after 24 h, the shaken flask, the rocker platform, and the 6-well shaker incubation systems appeared to be superior to the stirred well and the roller incubation systems. Chemicals/CAS: L-Lactate Dehydrogenase, EC 1.1.1.27; Potassium, 7440-09-7; Xenobiotics

Published
1997

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