Next Article in Journal
Reactive Oxygen Species and Abiotic Stress in Plants
Next Article in Special Issue
Biological Activity of c-Peptide in Microvascular Complications of Type 1 Diabetes—Time for Translational Studies or Back to the Basics?
Previous Article in Journal
The Discovery of Highly Potent THP Derivatives as OCTN2 Inhibitors: From Structure-Based Virtual Screening to In Vivo Biological Activity
Article

Role of TSPO/VDAC1 Upregulation and Matrix Metalloproteinase-2 Localization in the Dysfunctional Myocardium of Hyperglycaemic Rats

1
IRC-FSH Department of Health Sciences, University “Magna Græcia” of Catanzaro, 88100 Catanzaro, Italy
2
Renato Dulbecco Institute, Presso Fondazione Terina, 88046 Lamezia Terme (CZ), Italy
3
Division of Cardiology, University Hospital Policlinico Tor Vergata, 00133 Rome, Italy
4
IRCCS San Raffaele Pisana, Via di Valcannuta, 00163 Rome, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(20), 7432; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21207432
Received: 30 July 2020 / Revised: 6 September 2020 / Accepted: 25 September 2020 / Published: 9 October 2020
(This article belongs to the Special Issue Molecular Metabolic Regulation in Diabetes 2.0)
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. View Full-Text
Keywords: hyperglycaemia; superoxide anion; mitochondrial dysfunction; TSPO; VDAC1; MMP-2; MAM; cardiomyocyte; diabetes; myocardium hyperglycaemia; superoxide anion; mitochondrial dysfunction; TSPO; VDAC1; MMP-2; MAM; cardiomyocyte; diabetes; myocardium
Show Figures

Figure 1

MDPI and ACS Style

Gliozzi, M.; Scarano, F.; Musolino, V.; Carresi, C.; Scicchitano, M.; Ruga, S.; Zito, M.C.; Nucera, S.; Bosco, F.; Maiuolo, J.; Macrì, R.; Guarnieri, L.; Mollace, R.; Coppoletta, A.R.; Nicita, C.; Tavernese, A.; Palma, E.; Muscoli, C.; Mollace, V. Role of TSPO/VDAC1 Upregulation and Matrix Metalloproteinase-2 Localization in the Dysfunctional Myocardium of Hyperglycaemic Rats. Int. J. Mol. Sci. 2020, 21, 7432. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21207432

AMA Style

Gliozzi M, Scarano F, Musolino V, Carresi C, Scicchitano M, Ruga S, Zito MC, Nucera S, Bosco F, Maiuolo J, Macrì R, Guarnieri L, Mollace R, Coppoletta AR, Nicita C, Tavernese A, Palma E, Muscoli C, Mollace V. Role of TSPO/VDAC1 Upregulation and Matrix Metalloproteinase-2 Localization in the Dysfunctional Myocardium of Hyperglycaemic Rats. International Journal of Molecular Sciences. 2020; 21(20):7432. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21207432

Chicago/Turabian Style

Gliozzi, Micaela, Federica Scarano, Vincenzo Musolino, Cristina Carresi, Miriam Scicchitano, Stefano Ruga, Maria C. Zito, Saverio Nucera, Francesca Bosco, Jessica Maiuolo, Roberta Macrì, Lorenza Guarnieri, Rocco Mollace, Anna R. Coppoletta, Caterina Nicita, Annamaria Tavernese, Ernesto Palma, Carolina Muscoli, and Vincenzo Mollace. 2020. "Role of TSPO/VDAC1 Upregulation and Matrix Metalloproteinase-2 Localization in the Dysfunctional Myocardium of Hyperglycaemic Rats" International Journal of Molecular Sciences 21, no. 20: 7432. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21207432

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop