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Role of TSPO/VDAC1 Upregulation and Matrix Metalloproteinase-2 Localization in the Dysfunctional Myocardium of Hyperglycaemic Rats
Clinical management of diabetic cardiomyopathy represents an unmet need owing to insufficient knowledge about the molecular mechanisms underlying the dysfunctional heart. The aim of this work is to better clarify the role of matrix metalloproteinase 2 (MMP-2) isoforms and of translocator protein (TS...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587933/ https://www.ncbi.nlm.nih.gov/pubmed/33050121 http://dx.doi.org/10.3390/ijms21207432 |
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author | Gliozzi, Micaela Scarano, Federica Musolino, Vincenzo Carresi, Cristina Scicchitano, Miriam Ruga, Stefano Zito, Maria Caterina Nucera, Saverio Bosco, Francesca Maiuolo, Jessica Macrì, Roberta Guarnieri, Lorenza Mollace, Rocco Coppoletta, Anna Rita Nicita, Caterina Tavernese, Annamaria Palma, Ernesto Muscoli, Carolina Mollace, Vincenzo |
author_facet | Gliozzi, Micaela Scarano, Federica Musolino, Vincenzo Carresi, Cristina Scicchitano, Miriam Ruga, Stefano Zito, Maria Caterina Nucera, Saverio Bosco, Francesca Maiuolo, Jessica Macrì, Roberta Guarnieri, Lorenza Mollace, Rocco Coppoletta, Anna Rita Nicita, Caterina Tavernese, Annamaria Palma, Ernesto Muscoli, Carolina Mollace, Vincenzo |
author_sort | Gliozzi, Micaela |
collection | PubMed |
description | Clinical management of diabetic cardiomyopathy represents an unmet need owing to insufficient knowledge about the molecular mechanisms underlying the dysfunctional heart. The aim of this work is to better clarify the role of matrix metalloproteinase 2 (MMP-2) isoforms and of translocator protein (TSPO)/voltage-dependent anion-selective channel 1 (VDAC1) modulation in the development of hyperglycaemia-induced myocardial injury. Hyperglycaemia was induced in Sprague-Dawley rats through a streptozocin injection (35 mg/Kg, i.p.). After 60 days, cardiac function was analysed by echocardiography. Nicotinamide Adenine Dinucleotide Phosphate NADPH oxidase and TSPO expression was assessed by immunohistochemistry. MMP-2 activity was detected by zymography. Superoxide anion production was estimated by MitoSOX™ staining. Voltage-dependent anion-selective channel 1 (VDAC-1), B-cell lymphoma 2 (Bcl-2), and cytochrome C expression was assessed by Western blot. Hyperglycaemic rats displayed cardiac dysfunction; this response was characterized by an overexpression of NADPH oxidase, accompanied by an increase of superoxide anion production. Under hyperglycaemia, increased expression of TSPO and VDAC1 was detected. MMP-2 downregulated activity occurred under hyperglycemia and this profile of activation was accompanied by the translocation of intracellular N-terminal truncated isoform of MMP-2 (NT-MMP-2) from mitochondria-associated membrane (MAM) into mitochondria. In the onset of diabetic cardiomyopathy, mitochondrial impairment in cardiomyocytes is characterized by the dysregulation of the different MMP-2 isoforms. This can imply the generation of a “frail” myocardial tissue unable to adapt itself to stress. |
format | Online Article Text |
id | pubmed-7587933 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75879332020-10-29 Role of TSPO/VDAC1 Upregulation and Matrix Metalloproteinase-2 Localization in the Dysfunctional Myocardium of Hyperglycaemic Rats Gliozzi, Micaela Scarano, Federica Musolino, Vincenzo Carresi, Cristina Scicchitano, Miriam Ruga, Stefano Zito, Maria Caterina Nucera, Saverio Bosco, Francesca Maiuolo, Jessica Macrì, Roberta Guarnieri, Lorenza Mollace, Rocco Coppoletta, Anna Rita Nicita, Caterina Tavernese, Annamaria Palma, Ernesto Muscoli, Carolina Mollace, Vincenzo Int J Mol Sci Article Clinical management of diabetic cardiomyopathy represents an unmet need owing to insufficient knowledge about the molecular mechanisms underlying the dysfunctional heart. The aim of this work is to better clarify the role of matrix metalloproteinase 2 (MMP-2) isoforms and of translocator protein (TSPO)/voltage-dependent anion-selective channel 1 (VDAC1) modulation in the development of hyperglycaemia-induced myocardial injury. Hyperglycaemia was induced in Sprague-Dawley rats through a streptozocin injection (35 mg/Kg, i.p.). After 60 days, cardiac function was analysed by echocardiography. Nicotinamide Adenine Dinucleotide Phosphate NADPH oxidase and TSPO expression was assessed by immunohistochemistry. MMP-2 activity was detected by zymography. Superoxide anion production was estimated by MitoSOX™ staining. Voltage-dependent anion-selective channel 1 (VDAC-1), B-cell lymphoma 2 (Bcl-2), and cytochrome C expression was assessed by Western blot. Hyperglycaemic rats displayed cardiac dysfunction; this response was characterized by an overexpression of NADPH oxidase, accompanied by an increase of superoxide anion production. Under hyperglycaemia, increased expression of TSPO and VDAC1 was detected. MMP-2 downregulated activity occurred under hyperglycemia and this profile of activation was accompanied by the translocation of intracellular N-terminal truncated isoform of MMP-2 (NT-MMP-2) from mitochondria-associated membrane (MAM) into mitochondria. In the onset of diabetic cardiomyopathy, mitochondrial impairment in cardiomyocytes is characterized by the dysregulation of the different MMP-2 isoforms. This can imply the generation of a “frail” myocardial tissue unable to adapt itself to stress. MDPI 2020-10-09 /pmc/articles/PMC7587933/ /pubmed/33050121 http://dx.doi.org/10.3390/ijms21207432 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 Gliozzi, Micaela Scarano, Federica Musolino, Vincenzo Carresi, Cristina Scicchitano, Miriam Ruga, Stefano Zito, Maria Caterina Nucera, Saverio Bosco, Francesca Maiuolo, Jessica Macrì, Roberta Guarnieri, Lorenza Mollace, Rocco Coppoletta, Anna Rita Nicita, Caterina Tavernese, Annamaria Palma, Ernesto Muscoli, Carolina Mollace, Vincenzo Role of TSPO/VDAC1 Upregulation and Matrix Metalloproteinase-2 Localization in the Dysfunctional Myocardium of Hyperglycaemic Rats |
title | Role of TSPO/VDAC1 Upregulation and Matrix Metalloproteinase-2 Localization in the Dysfunctional Myocardium of Hyperglycaemic Rats |
title_full | Role of TSPO/VDAC1 Upregulation and Matrix Metalloproteinase-2 Localization in the Dysfunctional Myocardium of Hyperglycaemic Rats |
title_fullStr | Role of TSPO/VDAC1 Upregulation and Matrix Metalloproteinase-2 Localization in the Dysfunctional Myocardium of Hyperglycaemic Rats |
title_full_unstemmed | Role of TSPO/VDAC1 Upregulation and Matrix Metalloproteinase-2 Localization in the Dysfunctional Myocardium of Hyperglycaemic Rats |
title_short | Role of TSPO/VDAC1 Upregulation and Matrix Metalloproteinase-2 Localization in the Dysfunctional Myocardium of Hyperglycaemic Rats |
title_sort | role of tspo/vdac1 upregulation and matrix metalloproteinase-2 localization in the dysfunctional myocardium of hyperglycaemic rats |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587933/ https://www.ncbi.nlm.nih.gov/pubmed/33050121 http://dx.doi.org/10.3390/ijms21207432 |
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