RGD Reference Report - S 35171 exerts protective effects in spontaneously hypertensive stroke-prone rats by preserving mitochondrial function. - Rat Genome Database

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S 35171 exerts protective effects in spontaneously hypertensive stroke-prone rats by preserving mitochondrial function.

Authors: Gelosa, P  Banfi, C  Brioschi, M  Nobili, E  Gianella, A  Guerrini, U  Pignieri, A  Tremoli, E  Sironi, L 
Citation: Gelosa P, etal., Eur J Pharmacol. 2009 Feb 14;604(1-3):117-24. Epub 2008 Dec 24.
RGD ID: 2303405
Pubmed: PMID:19135993   (View Abstract at PubMed)
DOI: DOI:10.1016/j.ejphar.2008.12.027   (Journal Full-text)

S 35171 is one of a family of compounds that have been designed to protect mitochondrial function. We tested the hypothesis that S 35171 exerts protective effects in spontaneously hypertensive stroke-prone rats (SHRSPs), an animal model developing spontaneous brain damage preceded by proteinuria and systemic inflammation revealed by the urinary accumulation of acute-phase proteins (APPs) originating in the liver. Male SHRSPs fed a permissive diet received vehicle or S 35171 (10 mg/kg/day) started simultaneously with a high-sodium diet (group A) or after the establishment of proteinuria (group B). The drug delayed urinary APPs accumulation and the appearance of magnetic resonance imaging (MRI)-monitored brain lesions (after 62+/-3 days in group A, and 51+/-2 days in controls, P<0.01). The delay was more pronounced in group B as 30% of the animals survived the entire 90-day experimental period without brain abnormality. Proteomic analysis showed no significant alteration in the expression pattern of brain mitochondrial proteins, but the liver mitochondrial levels of carbamoylphosphate synthase I (CPS-I), an enzyme involved in urea metabolism) and the antioxidant peroxiredoxin-3 spot were affected by hypertension and S 35171. Stress reduces CPS-I and induces the peroxiredoxin-3 spot, whereas S 35171 brought about normal CPS-I expression and a 12-fold higher level of the peroxiredoxin-3 spot. As both enzymes are involved in maintaining mitochondrial functions, their increased expression after S 35171 treatment may be responsible for delaying the pathological condition that leads to the development of brain damage in SHRSPs.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CPS1Humanhypertension  ISOCps1 (Rattus norvegicus)protein:decreased expression:liver and mitochondrionRGD 
Cps1Rathypertension  IEP protein:decreased expression:liver and mitochondrionRGD 
Cps1Mousehypertension  ISOCps1 (Rattus norvegicus)protein:decreased expression:liver and mitochondrionRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cps1Ratresponse to xenobiotic stimulus  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cps1  (carbamoyl-phosphate synthase 1)

Genes (Mus musculus)
Cps1  (carbamoyl-phosphate synthetase 1)

Genes (Homo sapiens)
CPS1  (carbamoyl-phosphate synthase 1)


Additional Information