title: Differential modulation of uncoupling protein 2 in kidneys of stroke-prone spontaneously hypertensive rats under high-salt/low-potassium diet.
abstract: The stroke-prone spontaneously hypertensive rat (SHRsp) represents an animal model of increased susceptibility to high-salt diet-induced cerebral and renal vascular injuries. High blood pressure and genetic factors are viewed as major contributing factors. In high-salt-loaded SHRsp and stroke-resistant SHR animals, we determined blood pressure levels, degree of kidney lesions, renal uncoupling protein 2 (UCP2) gene and protein expression levels along with rattus norvegicus (rno)-microRNA (miR) 24 and 34a gene expression, nuclear factor-κB protein levels, and oxidative stress. In vitro, UCP2 gene silencing was performed in renal mesangial cells. We found more severe degree of renal damage in SHRsp at the end of 4-week high-salt dietary treatment as compared with stroke-resistant SHR, despite comparable blood pressure levels, along with increased rate of inflammation and oxidative stress. Kidney UCP2 gene and protein expression levels were significantly downregulated under high-salt diet in SHRsp, but not in stroke-resistant SHR. Differential UCP2 regulation was paralleled by differential expression of kidney rno-miR 24 and 34a, known to target UCP2 gene, in the 2 strains. UCP2 gene silencing in renal mesangial cells led to increased rate of reactive oxygen species generation, increased inflammation and apoptosis, reduced cell vitality, and increased necrosis. In conclusion, high-salt diet downregulates the antioxidant UCP2-dependent mechanism in kidneys of SHRsp, but not of stroke-resistant SHR. A parallel differential kidney miR regulation under high-salt diet in the 2 strains may contribute to the differential UCP2 modulation. UCP2 is a critical protein to prevent oxidative stress damage in renal mesangial cells in vitro.
authors.affiliation: IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Di Castro
authors.forename: Stefania
authors.initials: S
authors.lastname: Scarpino
authors.forename: Simona
authors.initials: S
authors.lastname: Marchitti
authors.forename: Franca
authors.initials: F
authors.lastname: Bianchi
authors.forename: Rosita
authors.initials: R
authors.lastname: Stanzione
authors.forename: Maria
authors.initials: M
authors.lastname: Cotugno
authors.forename: Luigi
authors.initials: L
authors.lastname: Sironi
authors.forename: Paolo
authors.initials: P
authors.lastname: Gelosa
authors.forename: Enrico
authors.initials: E
authors.lastname: Duranti
authors.forename: Luigi
authors.initials: L
authors.lastname: Ruco
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
authors.forename: Speranza
authors.initials: S
authors.lastname: Rubattu
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D019175:DNA Methylation; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006973:Hypertension / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011401:Promoter Regions, Genetic; D051381:Rats; D011918:Rats, Inbred SHR; D017382:Reactive Oxygen Species / Q000378:metabolism; D017673:Sodium Chloride, Dietary; D020521:Stroke / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000071246:Uncoupling Protein 2
chemical_list: D007473:Ion Channels; C574736:MIRN24 microRNA, rat; C560944:MIRN34 microRNA, rat; D035683:MicroRNAs; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D017673:Sodium Chloride, Dietary; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2