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Proteome Analysis of Thyroid Hormone Transporter Mct8/Oatp1c1-Deficient Mice Reveals Novel Dysregulated Target Molecules Involved in Locomotor Function.
Siemes, Devon; Vancamp, Pieter; Markova, Boyka; Spangenberg, Philippa; Shevchuk, Olga; Siebels, Bente; Schlüter, Hartmut; Mayerl, Steffen; Heuer, Heike; Engel, Daniel Robert.
Afiliação
  • Siemes D; Department of Immunodynamics, Institute for Experimental Immunology and Imaging, University Duisburg-Essen, 45141 Essen, Germany.
  • Vancamp P; Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
  • Markova B; Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
  • Spangenberg P; Department of Immunodynamics, Institute for Experimental Immunology and Imaging, University Duisburg-Essen, 45141 Essen, Germany.
  • Shevchuk O; Department of Immunodynamics, Institute for Experimental Immunology and Imaging, University Duisburg-Essen, 45141 Essen, Germany.
  • Siebels B; Section Mass Spectrometric Proteomics, Diagnostic Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
  • Schlüter H; Section Mass Spectrometric Proteomics, Diagnostic Center, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
  • Mayerl S; Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
  • Heuer H; Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
  • Engel DR; Department of Immunodynamics, Institute for Experimental Immunology and Imaging, University Duisburg-Essen, 45141 Essen, Germany.
Cells ; 12(20)2023 10 19.
Article em En | MEDLINE | ID: mdl-37887331
Thyroid hormone (TH) transporter MCT8 deficiency causes severe locomotor disabilities likely due to insufficient TH transport across brain barriers and, consequently, compromised neural TH action. As an established animal model for this disease, Mct8/Oatp1c1 double knockout (DKO) mice exhibit strong central TH deprivation, locomotor impairments and similar histo-morphological features as seen in MCT8 patients. The pathways that cause these neuro-motor symptoms are poorly understood. In this paper, we performed proteome analysis of brain sections comprising cortical and striatal areas of 21-day-old WT and DKO mice. We detected over 2900 proteins by liquid chromatography mass spectrometry, 67 of which were significantly different between the genotypes. The comparison of the proteomic and published RNA-sequencing data showed a significant overlap between alterations in both datasets. In line with previous observations, DKO animals exhibited decreased myelin-associated protein expression and altered protein levels of well-established neuronal TH-regulated targets. As one intriguing new candidate, we unraveled and confirmed the reduced protein and mRNA expression of Pde10a, a striatal enzyme critically involved in dopamine receptor signaling, in DKO mice. As altered PDE10A activities are linked to dystonia, reduced basal ganglia PDE10A expression may represent a key pathogenic pathway underlying human MCT8 deficiency.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteoma / Simportadores Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteoma / Simportadores Idioma: En Ano de publicação: 2023 Tipo de documento: Article