RGD Reference Report - Obesity is associated with impaired ventricular protein kinase C-MAP kinase signaling and altered ANP mRNA expression in the heart of adult Zucker rats. - Rat Genome Database

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Obesity is associated with impaired ventricular protein kinase C-MAP kinase signaling and altered ANP mRNA expression in the heart of adult Zucker rats.

Authors: Morabito, D  Vallotton, MB  Lang, U 
Citation: Morabito D, etal., J Investig Med. 2001 Jul;49(4):310-8.
RGD ID: 1642533
Pubmed: PMID:11478406   (View Abstract at PubMed)
DOI: DOI:10.2310/6650.2001.33895   (Journal Full-text)

BACKGROUND: In the obesity model of the Zucker rat, myocardial protein kinase C (PKC) activation by phorbol ester is impaired. The influence of obesity on myocardial cell signaling was investigated by studying the activation of PKC isozymes and MAP kinases (MAPK) p38 and p42/44 as well as the induction of ANP mRNA. METHODS: Isolated hearts obtained from 17-week-old lean and obese Zucker rats were perfused with 200 nM phorbol 12-myristate 13-acetate (PMA) at different time periods. Immunodetectable PKC isozymes, phosphorylated-MAPK, and ANP mRNA were determined by Western and Northern blots, respectively. RESULTS: PMA promoted a marked transient translocation of ventricular PKCalpha from the cytosol to the membranes within 10 minutes in lean rats, whereas it had a much weaker effect in obese rats. Moreover, PMA induced a significant activation of PKCdelta in lean but not in obese rat hearts. After PKC activation, increases in phosphorylation levels of myocardial p38 and p42 MAPK were approximately 3-fold higher in lean rats than in obese animals. Concerning the induction of ANP, PMA transiently tripled ANP mRNA within 60 minutes in lean but not in obese rats. CONCLUSIONS: In the genetically obese Zucker rat, the myocardial signal transduction cascade PKC-MAPK-ANP mRNA seems to be markedly impaired. It can be speculated that this abnormal cardiac cell signaling in obese rats reflects an early phase in the cardiac pathogenesis accompanying obesity.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PRKCDHumanobesity  ISOPrkcd (Rattus norvegicus)protein:decreased expression:heart ventricleRGD 
PrkcdRatobesity  IEP protein:decreased expression:heart ventricleRGD 
PrkcdMouseobesity  ISOPrkcd (Rattus norvegicus)protein:decreased expression:heart ventricleRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PrkcdRatresponse to organic cyclic compound  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Prkcd  (protein kinase C, delta)

Genes (Mus musculus)
Prkcd  (protein kinase C, delta)

Genes (Homo sapiens)
PRKCD  (protein kinase C delta)


Additional Information