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Brain Overexpression of Uncoupling Protein-2 (UCP2) Delays Renal Damage and Stroke Occurrence in Stroke-Prone Spontaneously Hypertensive Rats

The downregulation of uncoupling protein-2 (UCP2) is associated with increased brain and kidney injury in stroke-prone spontaneously hypertensive rats (SHRSP) fed with a Japanese style hypersodic diet (JD). Systemic overexpression of UCP2 reduces organ damage in JD-fed SHRSP. We examined the effect...

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Autores principales: Busceti, Carla L., Cotugno, Maria, Bianchi, Franca, Forte, Maurizio, Stanzione, Rosita, Marchitti, Simona, Battaglia, Giuseppe, Nicoletti, Ferdinando, Fornai, Francesco, Rubattu, Speranza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352594/
https://www.ncbi.nlm.nih.gov/pubmed/32560241
http://dx.doi.org/10.3390/ijms21124289
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author Busceti, Carla L.
Cotugno, Maria
Bianchi, Franca
Forte, Maurizio
Stanzione, Rosita
Marchitti, Simona
Battaglia, Giuseppe
Nicoletti, Ferdinando
Fornai, Francesco
Rubattu, Speranza
author_facet Busceti, Carla L.
Cotugno, Maria
Bianchi, Franca
Forte, Maurizio
Stanzione, Rosita
Marchitti, Simona
Battaglia, Giuseppe
Nicoletti, Ferdinando
Fornai, Francesco
Rubattu, Speranza
author_sort Busceti, Carla L.
collection PubMed
description The downregulation of uncoupling protein-2 (UCP2) is associated with increased brain and kidney injury in stroke-prone spontaneously hypertensive rats (SHRSP) fed with a Japanese style hypersodic diet (JD). Systemic overexpression of UCP2 reduces organ damage in JD-fed SHRSP. We examined the effect of brain-specific UCP2 overexpression on blood pressure (BP), stroke occurrence and kidney damage in JD-fed SHRSP. Rats received a single i.c.v. injection of a lentiviral vector encoding UCP2 (LV-UCP2), or an empty vector. The brain delivery of LV-UCP2 significantly delayed the occurrence of stroke and kidney damage. The large reduction of proteinuria observed after LV-UCP2 injection was unexpected, because BP levels were unchanged. At the time of stroke, rats treated with LV-UCP2 still showed a large UCP2 upregulation in the striatum, associated with increases in OPA1 and FIS1 protein levels, and reductions in PGC1-α, SOD2, TNFα mRNA levels and NRF2 protein levels. This suggested UCP2 overexpression enhanced mitochondrial fusion and fission and reduced oxidative damage and inflammation in the striatum of JD-fed SHRSP rats. Our data suggest the existence of central mechanisms that may protect against hypertension-induced organ damage independently of BP, and strengthen the suitability of strategies aimed at enhancing UCP2 expression for the treatment of hypertensive damage.
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spelling pubmed-73525942020-07-15 Brain Overexpression of Uncoupling Protein-2 (UCP2) Delays Renal Damage and Stroke Occurrence in Stroke-Prone Spontaneously Hypertensive Rats Busceti, Carla L. Cotugno, Maria Bianchi, Franca Forte, Maurizio Stanzione, Rosita Marchitti, Simona Battaglia, Giuseppe Nicoletti, Ferdinando Fornai, Francesco Rubattu, Speranza Int J Mol Sci Article The downregulation of uncoupling protein-2 (UCP2) is associated with increased brain and kidney injury in stroke-prone spontaneously hypertensive rats (SHRSP) fed with a Japanese style hypersodic diet (JD). Systemic overexpression of UCP2 reduces organ damage in JD-fed SHRSP. We examined the effect of brain-specific UCP2 overexpression on blood pressure (BP), stroke occurrence and kidney damage in JD-fed SHRSP. Rats received a single i.c.v. injection of a lentiviral vector encoding UCP2 (LV-UCP2), or an empty vector. The brain delivery of LV-UCP2 significantly delayed the occurrence of stroke and kidney damage. The large reduction of proteinuria observed after LV-UCP2 injection was unexpected, because BP levels were unchanged. At the time of stroke, rats treated with LV-UCP2 still showed a large UCP2 upregulation in the striatum, associated with increases in OPA1 and FIS1 protein levels, and reductions in PGC1-α, SOD2, TNFα mRNA levels and NRF2 protein levels. This suggested UCP2 overexpression enhanced mitochondrial fusion and fission and reduced oxidative damage and inflammation in the striatum of JD-fed SHRSP rats. Our data suggest the existence of central mechanisms that may protect against hypertension-induced organ damage independently of BP, and strengthen the suitability of strategies aimed at enhancing UCP2 expression for the treatment of hypertensive damage. MDPI 2020-06-16 /pmc/articles/PMC7352594/ /pubmed/32560241 http://dx.doi.org/10.3390/ijms21124289 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
Busceti, Carla L.
Cotugno, Maria
Bianchi, Franca
Forte, Maurizio
Stanzione, Rosita
Marchitti, Simona
Battaglia, Giuseppe
Nicoletti, Ferdinando
Fornai, Francesco
Rubattu, Speranza
Brain Overexpression of Uncoupling Protein-2 (UCP2) Delays Renal Damage and Stroke Occurrence in Stroke-Prone Spontaneously Hypertensive Rats
title Brain Overexpression of Uncoupling Protein-2 (UCP2) Delays Renal Damage and Stroke Occurrence in Stroke-Prone Spontaneously Hypertensive Rats
title_full Brain Overexpression of Uncoupling Protein-2 (UCP2) Delays Renal Damage and Stroke Occurrence in Stroke-Prone Spontaneously Hypertensive Rats
title_fullStr Brain Overexpression of Uncoupling Protein-2 (UCP2) Delays Renal Damage and Stroke Occurrence in Stroke-Prone Spontaneously Hypertensive Rats
title_full_unstemmed Brain Overexpression of Uncoupling Protein-2 (UCP2) Delays Renal Damage and Stroke Occurrence in Stroke-Prone Spontaneously Hypertensive Rats
title_short Brain Overexpression of Uncoupling Protein-2 (UCP2) Delays Renal Damage and Stroke Occurrence in Stroke-Prone Spontaneously Hypertensive Rats
title_sort brain overexpression of uncoupling protein-2 (ucp2) delays renal damage and stroke occurrence in stroke-prone spontaneously hypertensive rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352594/
https://www.ncbi.nlm.nih.gov/pubmed/32560241
http://dx.doi.org/10.3390/ijms21124289
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