Downregulation and nuclear relocation of MLP during the progression of right ventricular hypertrophy induced by chronic pressure overload. J Mol Cell Cardiol 2000 Dec;32(12):2385-95
Date
12/13/2000Pubmed ID
11113014DOI
10.1006/jmcc.2000.1269Scopus ID
2-s2.0-0034509337 (requires institutional sign-in at Scopus site) 53 CitationsAbstract
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.
Author List
Ecarnot-Laubriet A, De Luca K, Vandroux D, Moisant M, Bernard C, Assem M, Rochette L, Teyssier JRAuthor
Mahfoud Assem PharmD Associate Professor in the School of Pharmacy Administration department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCardiomegaly
Cell Nucleus
Cytoplasm
Cytosol
Down-Regulation
Heart Ventricles
Homeodomain Proteins
Immunohistochemistry
LIM Domain Proteins
Lung
Male
Microscopy, Electron
Muscle Proteins
Myocardium
Myofibrils
Pressure
RNA, Messenger
Rats
Rats, Wistar
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Transcription, Genetic
Ventricular Function
