Lipopolysaccharide upregulates uPA, MMP-2 and MMP-9 via ERK1/2 signaling in H9c2 cardiomyoblast cells
ABSTRACT Upregulation of urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), and matrix metallopeptidases (MMPs) is associated with the development of myocardial infarction (MI), dilated cardiomyopathy, cardiac fibrosis, and heart failure (HF). Evidences suggest that lipopolysaccharide (LPS) participates in the inflammatory response in the cardiovascular system; however, it is unknown if LPS is sufficient to upregulate expressions and/or activity of uPA, tPA, MMP-2, and MMP-9 in myocardial cells. In this study, we treated H9c2 cardiomyoblasts with LPS to explore whether LPS upregulates uPA, tPA, MMP-2, and MMP-9, and further to identify the precise molecular and cellular mechanisms behind this upregulatory responses. Here, we show that LPS challenge increased the protein levels of uPA, MMP-2 and MMP-9, and induced the activity of MMP-2 and MMP-9 in H9c2 cardiomyoblasts. However, LPS showed no effects on the expression of tissue inhibitor of metalloproteinase-1, -2, -3, and -4 (TIMP-1, -2, -3, and -4). After administration of inhibitors including U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor), CsA (calcineurin inhibitor), and QNZ (NFkappaB inhibitor), the LPS-upregulated expression and/or activity of uPA, MMP-2, and MMP-9 in H9c2 cardiomyoblasts are markedly inhibited only by ERK1/2 inhibitors, U0126. Collectively, these results suggest that LPS upregulates the expression and/or activity of uPA, MMP-2, and MMP-9 through ERK1/2 signaling pathway in H9c2 cardiomyoblasts. Our findings further provide a link between the LPS-induced cardiac dysfunction and the ERK1/2 signaling pathway that mediates the upregulation of uPA, MMP-2 and MMP-9.
- SourceAvailable from: Stephen Tzang
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- "Mitogen-activated protein kinases (MAPKs) include three major subfamilies such as the extracellularly responsive kinases (ERKs), the c-Jun N-terminal kinases (JNKs), also known as stress-activated protein kinases (SAPKs), and the p38 MAPKs . In the heart, MAPK signaling pathways have been reported to participate in the development of cardiac hypertrophy in response to stimuli   . For example, depletion of ERK1/2 signaling pathway using antisense oligodeoxynucleotides significantly attenuated phenylephrine (PE)-induced cardiomyocyte hypertrophy in culture . "
ABSTRACT: Garlic oil has been reported to protect the cardiovascular system; however, the effects and mechanisms behind the cardioprotection of garlic oil on diabetes-induced cardiaomyopathy are unclear. In this study, we used streptozotocin (STZ)-induced diabetic rats to investigate whether garlic oil could protect the heart from diabetes-induced cardiomyopathy. Wistar STZ-induced diabetic rats received garlic oil (0, 10, 50 or 100 mg kg −1 body weight) by gastric gavage every 2 days for 16 days. Normal rats without diabetes were used as control. Cardiac contractile dysfunction and cardiac pathologic hypertrophy responses were observed in diabetic rat hearts. Cardiac function was examined using echocardiography. In addition to cardiac hypertrophy-related mitogen-activated protein kinases (MAPK) pathways (e.g., p38, c-Jun N-terminal kinases (JNK) and extracellularly responsive kinase (ERK1/2)), the IL-6/MEK5/ERK5 signaling pathway was greatly activated in the diabetic rat hearts, which contributes to the up-regulation of cardiac pathologic hypertrophy markers including atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), and leads to cardiac contractile dysfunction. Garlic oil treatment significantly inhibited the up-regulation in MAPK (e.g., p38, JNK and ERK1/2) and IL-6/MEK5/ERK5 signaling pathways in the diabetic rat hearts, reducing the levels of cardiac pathologic hypertrophy markers such as ANP and BNP, and improving the cardiac contractile function. Collectively, data from these studies demonstrate that garlic oil shows the potential cardioprotective effects for protecting heart from diabetic cardiomyopathy.Evidence-based Complementary and Alternative Medicine 01/2011; 2011(1741-427X):950150. DOI:10.1093/ecam/neq075 · 1.88 Impact Factor
Article: Oxidative conversions of biphenylene[Show abstract] [Hide abstract]
ABSTRACT: form only given. The study of the reactions of tricyclic aromatic hydrocarbon biphenylene (bph) is of interest owing to the potential production of a superconducting polymer on its base. Bph was found to be polymerized under the action of aluminium chloride in noncoordinating solvents with the formation of a polymer with an irregular structure containing at least three types of structural fragments. The interaction of bph with Pd(CF/sub 3/COO)/sub 2/ (A) in CF/sub 3/COOH leads to the cleavage of C-C bond of bph cyclobutane ring and the formation of o-polyphenylens modified with (A). Its formation was confirmed by using elemental analysis, IR- and XP-spectroscopy. In both cases the polymers formed were nonconducting. Galvanostatic oxidation of bph was carried out on platinum electrode (S=/sub 2/cm/sup 2/) at current density i=1-1,/sub 2/mA/cm/sup 2/ in anhydrous oxygen free 0,05M Bu/sub 4/NBF/sub 4/ solution in CH/sub 2/Cl/sub 2/. It was found that a black coating with /spl sigma/ and g-factor equal to 10/sup -4/cm/sup -1/om/sup -1/ and 2,0028 respectively was deposited onto electrode surface. Its elemental analysis is in accordance with stoichiometric formula (C/sub 6/H/sub 4/)/sub 3/(BF/sub 4/)/sub 2/and evidences the destruction of biphenylene molecules during the electrolysis.
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ABSTRACT: Matrix metalloproteinases (MMPs, matrixins) are a family of secreted and membrane-bound zinc-dependent endopeptidases that have the combined capacity to degrade all the components of the extracellular matrix. These enzymes have a common zinc-binding motif (HEXXHXXGXXH) in their active site and a conserved methionine turn following the active site. MMP enzymes are strongly involved in a kaleidoscope of normal, pathological, physiological, and biological processes such as embryogenesis, normal tissue remodeling, wound healing, and angiogenesis, and in diseases such as atheroma, arthritis, cancer, and tissue ulceration. MMPs play a significant role in vascular remodeling. Broad-spectrum metalloproteinase inhibitors as potential therapeutics have been developed to explore the involvement of MMPs in various diseases.