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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MDPI AG
2020-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/12/4289 |
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| author | Carla L. Busceti Maria Cotugno Franca Bianchi Maurizio Forte Rosita Stanzione Simona Marchitti Giuseppe Battaglia Ferdinando Nicoletti Francesco Fornai Speranza Rubattu |
| author_facet | Carla L. Busceti Maria Cotugno Franca Bianchi Maurizio Forte Rosita Stanzione Simona Marchitti Giuseppe Battaglia Ferdinando Nicoletti Francesco Fornai Speranza Rubattu |
| author_sort | Carla L. Busceti |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T19:07:39Z |
| format | Article |
| id | doaj.art-02c76c0d92534eb2841bdbebd5b5a205 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T19:07:39Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-02c76c0d92534eb2841bdbebd5b5a2052023-11-20T04:01:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-012112428910.3390/ijms21124289Brain Overexpression of Uncoupling Protein-2 (UCP2) Delays Renal Damage and Stroke Occurrence in Stroke-Prone Spontaneously Hypertensive RatsCarla L. Busceti0Maria Cotugno1Franca Bianchi2Maurizio Forte3Rosita Stanzione4Simona Marchitti5Giuseppe Battaglia6Ferdinando Nicoletti7Francesco Fornai8Speranza Rubattu9IRCCS Neuromed, 86077 Pozzilli, ItalyIRCCS Neuromed, 86077 Pozzilli, ItalyIRCCS Neuromed, 86077 Pozzilli, ItalyIRCCS Neuromed, 86077 Pozzilli, ItalyIRCCS Neuromed, 86077 Pozzilli, ItalyIRCCS Neuromed, 86077 Pozzilli, ItalyIRCCS Neuromed, 86077 Pozzilli, ItalyIRCCS Neuromed, 86077 Pozzilli, ItalyIRCCS Neuromed, 86077 Pozzilli, ItalyIRCCS Neuromed, 86077 Pozzilli, ItalyThe 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.https://www.mdpi.com/1422-0067/21/12/4289UCP2mitochondriabrainstrokerenal damagestroke-prone spontaneously hypertensive rat |
| spellingShingle | Carla L. Busceti Maria Cotugno Franca Bianchi Maurizio Forte Rosita Stanzione Simona Marchitti Giuseppe Battaglia Ferdinando Nicoletti Francesco Fornai Speranza Rubattu Brain Overexpression of Uncoupling Protein-2 (UCP2) Delays Renal Damage and Stroke Occurrence in Stroke-Prone Spontaneously Hypertensive Rats International Journal of Molecular Sciences UCP2 mitochondria brain stroke renal damage stroke-prone spontaneously hypertensive rat |
| 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 | UCP2 mitochondria brain stroke renal damage stroke-prone spontaneously hypertensive rat |
| url | https://www.mdpi.com/1422-0067/21/12/4289 |
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