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.

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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.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
PRKCD	Human	obesity		ISO	Prkcd (Rattus norvegicus)	protein:decreased expression:heart ventricle	RGD
Prkcd	Rat	obesity		IEP		protein:decreased expression:heart ventricle	RGD
Prkcd	Mouse	obesity		ISO	Prkcd (Rattus norvegicus)	protein:decreased expression:heart ventricle	RGD

Biological Process

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Prkcd	Rat	response to phorbol 13-acetate 12-myristate		IEP			RGD

Genes (Rattus norvegicus)


Prkcd (protein kinase C, delta)

Genes (Mus musculus)


Prkcd (protein kinase C, delta)

Genes (Homo sapiens)


PRKCD (protein kinase C delta)

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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.