Reduced brain UCP2 expression mediated by microRNA-503 contributes to increased stroke susceptibility in the high-salt fed stroke-prone spontaneously hypertensive rat

Speranza Rubattu, Rosita Stanzione, Franca Bianchi, Maria Cotugno, Maurizio Forte, Floriana Della Ragione, Salvatore Fioriniello, Maurizio D'Esposito, Simona Marchitti, Michele Madonna, Simona Baima, Giorgio Morelli, Sebastiano Sciarretta, Luigi Sironi, Paolo Gelosa, Massimo Volpe

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

UCP2 maps nearby the lod score peak of STR1-stroke QTL in the SHRSP rat strain. We explored the potential contribution of UCP2 to the high-salt diet (JD)-dependent increased stroke susceptibility of SHRSP. Male SHRSP, SHRSR, two reciprocal SHRSR/SHRSP-STR1/QTL stroke congenic lines received JD for 4 weeks to detect brain UCP2 gene/protein modulation as compared with regular diet (RD). Brains were also analyzed for NF-κB protein expression, oxidative stress level and UCP2-targeted microRNAs expression level. Next, based on knowledge that fenofibrate and Brassica Oleracea (BO) stimulate UCP2 expression through PPARα activation, we monitored stroke occurrence in SHRSP receiving JD plus fenofibrate versus vehicle, JD plus BO juice versus BO juice plus PPARα inhibitor. Brain UCP2 expression was markedly reduced by JD in SHRSP and in the (SHRsr.SHRsp-(D1Rat134-Mt1pa)) congenic line, whereas NF-κB expression and oxidative stress level increased. The opposite phenomenon was observed in the SHRSR and in the (SHRsp.SHRsr-(D1Rat134-Mt1pa)) reciprocal congenic line. Interestingly, the UCP2-targeted rno-microRNA-503 was significantly upregulated in SHRSP and decreased in SHRSR upon JD, with consistent changes in the two reciprocal congenic lines. Both fenofibrate and BO significantly decreased brain microRNA-503 level, upregulated UCP2 expression and protected SHRSP from stroke occurrence. In vitro overexpression of microRNA-503 in endothelial cells suppressed UCP2 expression and led to a significant increase of cell mortality with decreased cell viability. Brain UCP2 downregulation is a determinant of increased stroke predisposition in high-salt-fed SHRSP. In this context, UCP2 can be modulated by both pharmacological and nutraceutical agents. The microRNA-503 significantly contributes to mediate brain UCP2 downregulation in JD-fed SHRSP.

Original languageEnglish
Pages (from-to)e2891
JournalCell Death and Disease
Volume8
Issue number6
DOIs
Publication statusPublished - Jun 22 2017

Fingerprint

Inbred SHR Rats
MicroRNAs
Salts
Brassica
Stroke
Fenofibrate
Brain
Peroxisome Proliferator-Activated Receptors
Oxidative Stress
Down-Regulation
Diet
Lod Score
Dietary Supplements
Cell Survival
Endothelial Cells
Pharmacology
Mortality
Proteins

Keywords

  • Journal Article

Cite this

Reduced brain UCP2 expression mediated by microRNA-503 contributes to increased stroke susceptibility in the high-salt fed stroke-prone spontaneously hypertensive rat. / Rubattu, Speranza; Stanzione, Rosita; Bianchi, Franca; Cotugno, Maria; Forte, Maurizio; Della Ragione, Floriana; Fioriniello, Salvatore; D'Esposito, Maurizio; Marchitti, Simona; Madonna, Michele; Baima, Simona; Morelli, Giorgio; Sciarretta, Sebastiano; Sironi, Luigi; Gelosa, Paolo; Volpe, Massimo.

In: Cell Death and Disease, Vol. 8, No. 6, 22.06.2017, p. e2891.

Research output: Contribution to journalArticle

Rubattu, S, Stanzione, R, Bianchi, F, Cotugno, M, Forte, M, Della Ragione, F, Fioriniello, S, D'Esposito, M, Marchitti, S, Madonna, M, Baima, S, Morelli, G, Sciarretta, S, Sironi, L, Gelosa, P & Volpe, M 2017, 'Reduced brain UCP2 expression mediated by microRNA-503 contributes to increased stroke susceptibility in the high-salt fed stroke-prone spontaneously hypertensive rat', Cell Death and Disease, vol. 8, no. 6, pp. e2891. https://doi.org/10.1038/cddis.2017.278
Rubattu, Speranza ; Stanzione, Rosita ; Bianchi, Franca ; Cotugno, Maria ; Forte, Maurizio ; Della Ragione, Floriana ; Fioriniello, Salvatore ; D'Esposito, Maurizio ; Marchitti, Simona ; Madonna, Michele ; Baima, Simona ; Morelli, Giorgio ; Sciarretta, Sebastiano ; Sironi, Luigi ; Gelosa, Paolo ; Volpe, Massimo. / Reduced brain UCP2 expression mediated by microRNA-503 contributes to increased stroke susceptibility in the high-salt fed stroke-prone spontaneously hypertensive rat. In: Cell Death and Disease. 2017 ; Vol. 8, No. 6. pp. e2891.
@article{05f88a2207614292b265c82a96bb19ab,
title = "Reduced brain UCP2 expression mediated by microRNA-503 contributes to increased stroke susceptibility in the high-salt fed stroke-prone spontaneously hypertensive rat",
abstract = "UCP2 maps nearby the lod score peak of STR1-stroke QTL in the SHRSP rat strain. We explored the potential contribution of UCP2 to the high-salt diet (JD)-dependent increased stroke susceptibility of SHRSP. Male SHRSP, SHRSR, two reciprocal SHRSR/SHRSP-STR1/QTL stroke congenic lines received JD for 4 weeks to detect brain UCP2 gene/protein modulation as compared with regular diet (RD). Brains were also analyzed for NF-κB protein expression, oxidative stress level and UCP2-targeted microRNAs expression level. Next, based on knowledge that fenofibrate and Brassica Oleracea (BO) stimulate UCP2 expression through PPARα activation, we monitored stroke occurrence in SHRSP receiving JD plus fenofibrate versus vehicle, JD plus BO juice versus BO juice plus PPARα inhibitor. Brain UCP2 expression was markedly reduced by JD in SHRSP and in the (SHRsr.SHRsp-(D1Rat134-Mt1pa)) congenic line, whereas NF-κB expression and oxidative stress level increased. The opposite phenomenon was observed in the SHRSR and in the (SHRsp.SHRsr-(D1Rat134-Mt1pa)) reciprocal congenic line. Interestingly, the UCP2-targeted rno-microRNA-503 was significantly upregulated in SHRSP and decreased in SHRSR upon JD, with consistent changes in the two reciprocal congenic lines. Both fenofibrate and BO significantly decreased brain microRNA-503 level, upregulated UCP2 expression and protected SHRSP from stroke occurrence. In vitro overexpression of microRNA-503 in endothelial cells suppressed UCP2 expression and led to a significant increase of cell mortality with decreased cell viability. Brain UCP2 downregulation is a determinant of increased stroke predisposition in high-salt-fed SHRSP. In this context, UCP2 can be modulated by both pharmacological and nutraceutical agents. The microRNA-503 significantly contributes to mediate brain UCP2 downregulation in JD-fed SHRSP.",
keywords = "Journal Article",
author = "Speranza Rubattu and Rosita Stanzione and Franca Bianchi and Maria Cotugno and Maurizio Forte and {Della Ragione}, Floriana and Salvatore Fioriniello and Maurizio D'Esposito and Simona Marchitti and Michele Madonna and Simona Baima and Giorgio Morelli and Sebastiano Sciarretta and Luigi Sironi and Paolo Gelosa and Massimo Volpe",
year = "2017",
month = "6",
day = "22",
doi = "10.1038/cddis.2017.278",
language = "English",
volume = "8",
pages = "e2891",
journal = "Cell Death and Disease",
issn = "2041-4889",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Reduced brain UCP2 expression mediated by microRNA-503 contributes to increased stroke susceptibility in the high-salt fed stroke-prone spontaneously hypertensive rat

AU - Rubattu, Speranza

AU - Stanzione, Rosita

AU - Bianchi, Franca

AU - Cotugno, Maria

AU - Forte, Maurizio

AU - Della Ragione, Floriana

AU - Fioriniello, Salvatore

AU - D'Esposito, Maurizio

AU - Marchitti, Simona

AU - Madonna, Michele

AU - Baima, Simona

AU - Morelli, Giorgio

AU - Sciarretta, Sebastiano

AU - Sironi, Luigi

AU - Gelosa, Paolo

AU - Volpe, Massimo

PY - 2017/6/22

Y1 - 2017/6/22

N2 - UCP2 maps nearby the lod score peak of STR1-stroke QTL in the SHRSP rat strain. We explored the potential contribution of UCP2 to the high-salt diet (JD)-dependent increased stroke susceptibility of SHRSP. Male SHRSP, SHRSR, two reciprocal SHRSR/SHRSP-STR1/QTL stroke congenic lines received JD for 4 weeks to detect brain UCP2 gene/protein modulation as compared with regular diet (RD). Brains were also analyzed for NF-κB protein expression, oxidative stress level and UCP2-targeted microRNAs expression level. Next, based on knowledge that fenofibrate and Brassica Oleracea (BO) stimulate UCP2 expression through PPARα activation, we monitored stroke occurrence in SHRSP receiving JD plus fenofibrate versus vehicle, JD plus BO juice versus BO juice plus PPARα inhibitor. Brain UCP2 expression was markedly reduced by JD in SHRSP and in the (SHRsr.SHRsp-(D1Rat134-Mt1pa)) congenic line, whereas NF-κB expression and oxidative stress level increased. The opposite phenomenon was observed in the SHRSR and in the (SHRsp.SHRsr-(D1Rat134-Mt1pa)) reciprocal congenic line. Interestingly, the UCP2-targeted rno-microRNA-503 was significantly upregulated in SHRSP and decreased in SHRSR upon JD, with consistent changes in the two reciprocal congenic lines. Both fenofibrate and BO significantly decreased brain microRNA-503 level, upregulated UCP2 expression and protected SHRSP from stroke occurrence. In vitro overexpression of microRNA-503 in endothelial cells suppressed UCP2 expression and led to a significant increase of cell mortality with decreased cell viability. Brain UCP2 downregulation is a determinant of increased stroke predisposition in high-salt-fed SHRSP. In this context, UCP2 can be modulated by both pharmacological and nutraceutical agents. The microRNA-503 significantly contributes to mediate brain UCP2 downregulation in JD-fed SHRSP.

AB - UCP2 maps nearby the lod score peak of STR1-stroke QTL in the SHRSP rat strain. We explored the potential contribution of UCP2 to the high-salt diet (JD)-dependent increased stroke susceptibility of SHRSP. Male SHRSP, SHRSR, two reciprocal SHRSR/SHRSP-STR1/QTL stroke congenic lines received JD for 4 weeks to detect brain UCP2 gene/protein modulation as compared with regular diet (RD). Brains were also analyzed for NF-κB protein expression, oxidative stress level and UCP2-targeted microRNAs expression level. Next, based on knowledge that fenofibrate and Brassica Oleracea (BO) stimulate UCP2 expression through PPARα activation, we monitored stroke occurrence in SHRSP receiving JD plus fenofibrate versus vehicle, JD plus BO juice versus BO juice plus PPARα inhibitor. Brain UCP2 expression was markedly reduced by JD in SHRSP and in the (SHRsr.SHRsp-(D1Rat134-Mt1pa)) congenic line, whereas NF-κB expression and oxidative stress level increased. The opposite phenomenon was observed in the SHRSR and in the (SHRsp.SHRsr-(D1Rat134-Mt1pa)) reciprocal congenic line. Interestingly, the UCP2-targeted rno-microRNA-503 was significantly upregulated in SHRSP and decreased in SHRSR upon JD, with consistent changes in the two reciprocal congenic lines. Both fenofibrate and BO significantly decreased brain microRNA-503 level, upregulated UCP2 expression and protected SHRSP from stroke occurrence. In vitro overexpression of microRNA-503 in endothelial cells suppressed UCP2 expression and led to a significant increase of cell mortality with decreased cell viability. Brain UCP2 downregulation is a determinant of increased stroke predisposition in high-salt-fed SHRSP. In this context, UCP2 can be modulated by both pharmacological and nutraceutical agents. The microRNA-503 significantly contributes to mediate brain UCP2 downregulation in JD-fed SHRSP.

KW - Journal Article

U2 - 10.1038/cddis.2017.278

DO - 10.1038/cddis.2017.278

M3 - Article

C2 - 28640254

VL - 8

SP - e2891

JO - Cell Death and Disease

JF - Cell Death and Disease

SN - 2041-4889

IS - 6

ER -