RGD Reference Report - Downregulation and nuclear relocation of MLP during the progression of right ventricular hypertrophy induced by chronic pressure overload. - Rat Genome Database

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Downregulation and nuclear relocation of MLP during the progression of right ventricular hypertrophy induced by chronic pressure overload.

Authors: Ecarnot-Laubriet, A  De Luca, K  Vandroux, D  Moisant, M  Bernard, C  Assem, M  Rochette, L  Teyssier, JR 
Citation: Ecarnot-Laubriet A, etal., J Mol Cell Cardiol. 2000 Dec;32(12):2385-95.
RGD ID: 1598503
Pubmed: PMID:11113014   (View Abstract at PubMed)
DOI: DOI:10.1006/jmcc.2000.1269   (Journal Full-text)

The cardiac LIM domain protein MLP plays a crucial role in the architecture and mechanical function of cardiac myocytes. Mice lacking the MLP gene develop cardiac hypertrophy, dilated cardiopathy and heart failure. We investigated whether downregulation of MLP is induced by pressure overload and contributes to the physiopathology of cardiac hypertrophy and failure. We studied this mechanism in rat right ventricles submitted to pulmonary arterial hypertension, because it is known that this ventricle is very vulnerable to the deleterious effects of pressure overload. During the progression of cardiac hypertrophy to failure over a 31 days period there was a dramatic decrease by 50% of the MLP transcripts level. Consistently, immunohistochemistry detected very weak protein signals in the cytoplasms of cardiomyocytes at the failing stage, but myocytes nuclei were heavily labeled. The nuclear relocation was confirmed by the immunodetection of MLP on the nuclear and cytosolic fractions. This nuclear localization is the hallmark of a retro-differentiated phenotype, since it has been observed only in differentiating myoblasts. These changes were associated with ultrastructural disorganization of the myofibrils similar to that observed in MLP -/- mice. Therefore, MLP dowregulation occurring during gene reprogramming may critically contribute to mechanical failure of the myocardium.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Right Ventricular Hypertrophy  ISOCsrp3 (Rattus norvegicus)1598503; 1598503 RGD 
Right Ventricular Hypertrophy  IEP 1598503 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Csrp3  (cysteine and glycine rich protein 3)

Genes (Mus musculus)
Csrp3  (cysteine and glycine-rich protein 3)

Genes (Homo sapiens)
CSRP3  (cysteine and glycine rich protein 3)


Additional Information