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Regulation of Lipoma Preferred Partner in the heart
Author(s) -
Boateng Samuel,
Hooper Charlotte
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1134.7
Subject(s) - microbiology and biotechnology , downregulation and upregulation , signal transducing adaptor protein , myocyte , cytoskeleton , actin , pressure overload , actinin , microtubule , biology , chemistry , signal transduction , heart failure , medicine , cell , biochemistry , gene , cardiac hypertrophy
Adaptor proteins play an important role in signalling pathways by providing a platform on which many proteins interact. Malfunction or mislocalisation of these proteins play a role in the development of disease. Lipoma preferred partner (LPP) is a nucleocytoplasmic shuttling adaptor protein. Previous work show that LPP plays a role in the function of smooth muscle cells and in atherosclerosis. In this study we wanted to determine whether LPP has a role in the myocardium. LPP expression increased by 56% in hearts from pressure overload aortic banded rats (p<0.05 n=4), but not after myocardial infarction, suggesting mechanical regulation of its expression. In vitro, LPP expression was 87% higher in cardiac fibroblasts than myocytes (P<0.05 n=3). LPP expression was down‐regulated in the absence of the actin cytoskeleton but not when microtubules were disassembled. We mechanically stretched cardiac fibroblasts using the Flexcell 4000 for 48h (1Hz, 5% maximum strain), which decreased total LPP expression by 35% and membrane localization in subcellular fractions (P<0.05, n=5). LNAME, an inhibitor of NO synthase upregulated LPP expression but not smooth muscle actin. These findings suggest that LPP is regulated by a complex interplay between NO and mechanical cues and may play a role in heart failure induced by mechanical stress.