LEPTIN REGULATES MMP-2, TIMP-1 AND COLLAGEN SYNTHESIS VIA p38 MAPK IN HL-1 MURINE CARDIOMYOCYTES
Journal Title: Cellular and Molecular Biology Letters - Year 2010, Vol 15, Issue 4
Abstract
A clear association between obesity and heart failure exists and a significant role for leptin, the product of the obese gene, has been suggested. One aspect of myocardial remodeling which characterizes heart failure is a disruption in the balance of extracellular matrix synthesis and degradation. Here we investigated the effects of leptin on matrix metalloproteinase (MMP) activity, tissue inhibitor of metalloproteinase (TIMP) expression, as well as collagen synthesis in HL-1 cardiac muscle cells. Gelatin zymographic analysis of MMP activity in conditioned media showed that leptin enhanced MMP-2 activity in a dose- and time-dependent manner. Leptin is known to stimulate phosphorylation of p38 MAPK in cardiac cells and utilization of the p38 MAPK inhibitor, SB203580, demonstrated that this kinase also plays a role in regulating several extracellular matrix components, such that inhibition of p38 MAPK signaling prevented the leptin-induced increase in MMP-2 activation. We also observed that leptin enhanced collagen synthesis determined by both proline incorporation and picrosirius red staining of conditioned media. Pro-collagen type-I and pro-collagen type-III expression, measured by real-time PCR and Western blotting were also increased by leptin, effects which were again attenuated by SB203580. In summary, these results demonstrate the potential for leptin to play a role in mediating myocardial ECM remodeling and that the p38 MAPK pathway plays an important role in mediating these effects.
Authors and Affiliations
Kristin Schram, Sabrina De Girolamo, Siham Madani, Diana Munoz, Farah Thong , Gary Sweeney
Keywords
Related Articles
- EP ID EP84975
- DOI 10.2478/s11658-010-0027-z
- Views 176
- Downloads 0
THE INTERACTOME: PREDICTING THE PROTEIN-PROTEIN INTERACTIONS IN CELLS
The term Interactome describes the set of all molecular interactions in cells, especially in the context of protein-protein interactions. These interactions are crucial for most cellular processes, so the full representa...
THE MOLECULAR CLONING OF GLIAL FIBRILLARY ACIDIC PROTEIN IN Gekko japonicus AND ITS EXPRESSION CHANGES AFTER SPINAL CORD TRANSECTION
The glial fibrillary acidic protein (GFAP) is an astrocyte-speci?c member of the class III intermediate filament proteins. It is generally used as a specific marker of astrocytes in the central nervous system (CNS). We i...
TOLL-LIKE RECEPTORS AND THEIR ROLE IN CARCINOGENESIS AND ANTI-TUMOR TREATMENT
Toll-like receptors (TLRs) have been described as major components of the innate immune system, recognizing the conserved molecular structures found in the large groups of pathogens called pathogen-associated molecular p...
THE ANTIOXIDANT PROPERTIES OF CARNITINE in vitro
Many of the effects of carnitine are ascribed to its antioxidant properties. The aim of this study was to evaluate the antioxidant properties of carnitine in vitro. Carnitine was found to decolorize ABTS●+ , and to prote...
A NEW BSMV-BASED VECTOR WITH MODIFIED ß MOLECULE ALLOWS SIMULTANEOUS AND STABLE SILENCING OF TWO GENES
Virus-induced gene silencing is an important tool for functional gene analysis and the vector based on Barley stripe mosaic virus (BSMV) is widely used for the purpose in monocots. Of the tripartite BSMV genome, currentl...