Cargando…

Mitochondrial Dysfunction: A Common Hallmark Underlying Comorbidity between sIBM and Other Degenerative and Age-Related Diseases

Sporadic inclusion body myositis (sIBM) is an inflammatory myopathy associated, among others, with mitochondrial dysfunction. Similar molecular features are found in Alzheimer’s disease (AD) and Type 2 Diabetes Mellitus (T2DM), underlying potential comorbidity. This study aims to evaluate common cli...

Descripción completa

Detalles Bibliográficos
Autores principales: Catalán-García, Marc, García-García, Francesc Josep, Moreno-Lozano, Pedro J., Alcarraz-Vizán, Gema, Tort-Merino, Adrià, Milisenda, José César, Cantó-Santos, Judith, Barcos-Rodríguez, Tamara, Cardellach, Francesc, Lladó, Albert, Novials, Anna, Garrabou, Glòria, Grau-Junyent, Josep M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290779/
https://www.ncbi.nlm.nih.gov/pubmed/32413985
http://dx.doi.org/10.3390/jcm9051446
_version_ 1783545756154593280
author Catalán-García, Marc
García-García, Francesc Josep
Moreno-Lozano, Pedro J.
Alcarraz-Vizán, Gema
Tort-Merino, Adrià
Milisenda, José César
Cantó-Santos, Judith
Barcos-Rodríguez, Tamara
Cardellach, Francesc
Lladó, Albert
Novials, Anna
Garrabou, Glòria
Grau-Junyent, Josep M.
author_facet Catalán-García, Marc
García-García, Francesc Josep
Moreno-Lozano, Pedro J.
Alcarraz-Vizán, Gema
Tort-Merino, Adrià
Milisenda, José César
Cantó-Santos, Judith
Barcos-Rodríguez, Tamara
Cardellach, Francesc
Lladó, Albert
Novials, Anna
Garrabou, Glòria
Grau-Junyent, Josep M.
author_sort Catalán-García, Marc
collection PubMed
description Sporadic inclusion body myositis (sIBM) is an inflammatory myopathy associated, among others, with mitochondrial dysfunction. Similar molecular features are found in Alzheimer’s disease (AD) and Type 2 Diabetes Mellitus (T2DM), underlying potential comorbidity. This study aims to evaluate common clinical and molecular hallmarks among sIBM, AD, and T2DM. Comorbidity with AD was assessed in n = 14 sIBM patients by performing neuropsychological and cognitive tests, cranial magnetic resonance imaging, AD cerebrospinal fluid biomarkers (levels of amyloid beta, total tau, and phosphorylated tau at threonine-181), and genetic apolipoprotein E genotyping. In the same sIBM cohort, comorbidity with T2DM was assessed by collecting anthropometric measures and performing an oral glucose tolerance test and insulin determinations. Results were compared to the standard population and other myositis (n = 7 dermatomyositis and n = 7 polymyositis). Mitochondrial contribution into disease was tested by measurement of oxidative/anaerobic and oxidant/antioxidant balances, respiration fluxes, and enzymatic activities in sIBM fibroblasts subjected to different glucose levels. Comorbidity of sIBM with AD was not detected. Clinically, sIBM patients showed signs of misbalanced glucose homeostasis, similar to other myositis. Such misbalance was further confirmed at the molecular level by the metabolic inability of sIBM fibroblasts to adapt to different glucose conditions. Under the standard condition, sIBM fibroblasts showed decreased respiration (0.71 ± 0.08 vs. 1.06 ± 0.04 nmols O(2)/min; p = 0.024) and increased anaerobic metabolism (5.76 ± 0.52 vs. 3.79 ± 0.35 mM lactate; p = 0.052). Moreover, when glucose conditions were changed, sIBM fibroblasts presented decreased fold change in mitochondrial enzymatic activities (−12.13 ± 21.86 vs. 199.22 ± 62.52 cytochrome c oxidase/citrate synthase ratio; p = 0.017) and increased oxidative stress per mitochondrial activity (203.76 ± 82.77 vs. −69.55 ± 21.00; p = 0.047), underlying scarce metabolic plasticity. These findings do not demonstrate higher prevalence of AD in sIBM patients, but evidences of prediabetogenic conditions were found. Glucose deregulation in myositis suggests the contribution of lifestyle conditions, such as restricted mobility. Additionally, molecular evidences from sIBM fibroblasts confirm that mitochondrial dysfunction may play a role. Monitoring T2DM development and mitochondrial contribution to disease in myositis patients could set a path for novel therapeutic options.
format Online
Article
Text
id pubmed-7290779
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-72907792020-06-17 Mitochondrial Dysfunction: A Common Hallmark Underlying Comorbidity between sIBM and Other Degenerative and Age-Related Diseases Catalán-García, Marc García-García, Francesc Josep Moreno-Lozano, Pedro J. Alcarraz-Vizán, Gema Tort-Merino, Adrià Milisenda, José César Cantó-Santos, Judith Barcos-Rodríguez, Tamara Cardellach, Francesc Lladó, Albert Novials, Anna Garrabou, Glòria Grau-Junyent, Josep M. J Clin Med Article Sporadic inclusion body myositis (sIBM) is an inflammatory myopathy associated, among others, with mitochondrial dysfunction. Similar molecular features are found in Alzheimer’s disease (AD) and Type 2 Diabetes Mellitus (T2DM), underlying potential comorbidity. This study aims to evaluate common clinical and molecular hallmarks among sIBM, AD, and T2DM. Comorbidity with AD was assessed in n = 14 sIBM patients by performing neuropsychological and cognitive tests, cranial magnetic resonance imaging, AD cerebrospinal fluid biomarkers (levels of amyloid beta, total tau, and phosphorylated tau at threonine-181), and genetic apolipoprotein E genotyping. In the same sIBM cohort, comorbidity with T2DM was assessed by collecting anthropometric measures and performing an oral glucose tolerance test and insulin determinations. Results were compared to the standard population and other myositis (n = 7 dermatomyositis and n = 7 polymyositis). Mitochondrial contribution into disease was tested by measurement of oxidative/anaerobic and oxidant/antioxidant balances, respiration fluxes, and enzymatic activities in sIBM fibroblasts subjected to different glucose levels. Comorbidity of sIBM with AD was not detected. Clinically, sIBM patients showed signs of misbalanced glucose homeostasis, similar to other myositis. Such misbalance was further confirmed at the molecular level by the metabolic inability of sIBM fibroblasts to adapt to different glucose conditions. Under the standard condition, sIBM fibroblasts showed decreased respiration (0.71 ± 0.08 vs. 1.06 ± 0.04 nmols O(2)/min; p = 0.024) and increased anaerobic metabolism (5.76 ± 0.52 vs. 3.79 ± 0.35 mM lactate; p = 0.052). Moreover, when glucose conditions were changed, sIBM fibroblasts presented decreased fold change in mitochondrial enzymatic activities (−12.13 ± 21.86 vs. 199.22 ± 62.52 cytochrome c oxidase/citrate synthase ratio; p = 0.017) and increased oxidative stress per mitochondrial activity (203.76 ± 82.77 vs. −69.55 ± 21.00; p = 0.047), underlying scarce metabolic plasticity. These findings do not demonstrate higher prevalence of AD in sIBM patients, but evidences of prediabetogenic conditions were found. Glucose deregulation in myositis suggests the contribution of lifestyle conditions, such as restricted mobility. Additionally, molecular evidences from sIBM fibroblasts confirm that mitochondrial dysfunction may play a role. Monitoring T2DM development and mitochondrial contribution to disease in myositis patients could set a path for novel therapeutic options. MDPI 2020-05-13 /pmc/articles/PMC7290779/ /pubmed/32413985 http://dx.doi.org/10.3390/jcm9051446 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Catalán-García, Marc
García-García, Francesc Josep
Moreno-Lozano, Pedro J.
Alcarraz-Vizán, Gema
Tort-Merino, Adrià
Milisenda, José César
Cantó-Santos, Judith
Barcos-Rodríguez, Tamara
Cardellach, Francesc
Lladó, Albert
Novials, Anna
Garrabou, Glòria
Grau-Junyent, Josep M.
Mitochondrial Dysfunction: A Common Hallmark Underlying Comorbidity between sIBM and Other Degenerative and Age-Related Diseases
title Mitochondrial Dysfunction: A Common Hallmark Underlying Comorbidity between sIBM and Other Degenerative and Age-Related Diseases
title_full Mitochondrial Dysfunction: A Common Hallmark Underlying Comorbidity between sIBM and Other Degenerative and Age-Related Diseases
title_fullStr Mitochondrial Dysfunction: A Common Hallmark Underlying Comorbidity between sIBM and Other Degenerative and Age-Related Diseases
title_full_unstemmed Mitochondrial Dysfunction: A Common Hallmark Underlying Comorbidity between sIBM and Other Degenerative and Age-Related Diseases
title_short Mitochondrial Dysfunction: A Common Hallmark Underlying Comorbidity between sIBM and Other Degenerative and Age-Related Diseases
title_sort mitochondrial dysfunction: a common hallmark underlying comorbidity between sibm and other degenerative and age-related diseases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290779/
https://www.ncbi.nlm.nih.gov/pubmed/32413985
http://dx.doi.org/10.3390/jcm9051446
work_keys_str_mv AT catalangarciamarc mitochondrialdysfunctionacommonhallmarkunderlyingcomorbiditybetweensibmandotherdegenerativeandagerelateddiseases
AT garciagarciafrancescjosep mitochondrialdysfunctionacommonhallmarkunderlyingcomorbiditybetweensibmandotherdegenerativeandagerelateddiseases
AT morenolozanopedroj mitochondrialdysfunctionacommonhallmarkunderlyingcomorbiditybetweensibmandotherdegenerativeandagerelateddiseases
AT alcarrazvizangema mitochondrialdysfunctionacommonhallmarkunderlyingcomorbiditybetweensibmandotherdegenerativeandagerelateddiseases
AT tortmerinoadria mitochondrialdysfunctionacommonhallmarkunderlyingcomorbiditybetweensibmandotherdegenerativeandagerelateddiseases
AT milisendajosecesar mitochondrialdysfunctionacommonhallmarkunderlyingcomorbiditybetweensibmandotherdegenerativeandagerelateddiseases
AT cantosantosjudith mitochondrialdysfunctionacommonhallmarkunderlyingcomorbiditybetweensibmandotherdegenerativeandagerelateddiseases
AT barcosrodrigueztamara mitochondrialdysfunctionacommonhallmarkunderlyingcomorbiditybetweensibmandotherdegenerativeandagerelateddiseases
AT cardellachfrancesc mitochondrialdysfunctionacommonhallmarkunderlyingcomorbiditybetweensibmandotherdegenerativeandagerelateddiseases
AT lladoalbert mitochondrialdysfunctionacommonhallmarkunderlyingcomorbiditybetweensibmandotherdegenerativeandagerelateddiseases
AT novialsanna mitochondrialdysfunctionacommonhallmarkunderlyingcomorbiditybetweensibmandotherdegenerativeandagerelateddiseases
AT garrabougloria mitochondrialdysfunctionacommonhallmarkunderlyingcomorbiditybetweensibmandotherdegenerativeandagerelateddiseases
AT graujunyentjosepm mitochondrialdysfunctionacommonhallmarkunderlyingcomorbiditybetweensibmandotherdegenerativeandagerelateddiseases