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.

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. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 21:12(2020). [10.3390/ijms21124289]

Brain overexpression of uncoupling protein-2 (UCP2) delays renal damage and stroke occurrence in stroke-prone spontaneously hypertensive rats

Busceti, Carla L
Investigation
;
Cotugno, Maria
Methodology
;
Stanzione, Rosita
Methodology
;
Marchitti, Simona
Methodology
;
Battaglia, Giuseppe
Investigation
;
Nicoletti, Ferdinando
Supervision
;
Rubattu, Speranza
Conceptualization
2020

Abstract

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.
2020
UCP2; brain; mitochondria; renal damage; stroke; stroke-prone spontaneously hypertensive rat
01 Pubblicazione su rivista::01a Articolo in rivista
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. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 21:12(2020). [10.3390/ijms21124289]
File allegati a questo prodotto
File Dimensione Formato  
Busceti_Brain_2020.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 2.74 MB
Formato Adobe PDF
2.74 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1420381
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 11
  • ???jsp.display-item.citation.isi??? 11
social impact