monensin and sphingosine-1-phosphate

monensin has been researched along with sphingosine-1-phosphate* in 1 studies

Other Studies

1 other study(ies) available for monensin and sphingosine-1-phosphate

ArticleYear
Role for furin in tumor necrosis factor alpha-induced activation of the matrix metalloproteinase/sphingolipid mitogenic pathway.
    Molecular and cellular biology, 2007, Volume: 27, Issue:8

    Neutral sphingomyelinase (nSMase), the initial enzyme of the sphingolipid signaling pathway, is thought to play a key role in cellular responses to tumor necrosis factor alpha (TNF-alpha), such as inflammation, proliferation, and apoptosis. The mechanism of TNF-alpha-induced nSMase activation is only partly understood. Using biochemical, molecular, and pharmacological approaches, we found that nSMase activation triggered by TNF-alpha is required for TNF-alpha-induced proliferation and in turn requires a proteolytic cascade involving furin, membrane type 1 matrix metalloproteinase (MT1-MMP), and MMP2, and leading finally to extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and DNA synthesis, in smooth muscle cells (SMC) and fibroblasts. Pharmacological and molecular inhibitors of MMPs (batimastat), furin (alpha1-PDX inhibitor-transfected SMC), MT1-MMP (SMC overexpressing a catalytically inactive MT1-MMP), MMP2 (fibroblasts from MMP2(-/-) mice), and small interfering RNA (siRNA) strategies (siRNAs targeting furin, MT1-MMP, MMP2, and nSMase) resulted in near-complete inhibition of the activation of nSMase, sphingosine kinase-1, and ERK1/2 and of subsequent DNA synthesis. Exogenous MT1-MMP activated nSMase and SMC proliferation in normal but not in MMP2(-/-) fibroblasts, whereas exogenous MMP2 was active on both normal and MMP2(-/-) fibroblasts. Altogether these findings highlight a pivotal role for furin, MT1-MMP, and MMP2 in TNF-alpha-induced sphingolipid signaling, and they identify this system as a possible target to inhibit SMC proliferation in vascular diseases.

    Topics: Animals; Brefeldin A; Cell Proliferation; Ceramides; Enzyme Activation; Fibroblasts; Furin; Humans; Lysophospholipids; Matrix Metalloproteinase 14; Matrix Metalloproteinase 2; Mice; Mitogens; Models, Biological; Monensin; Myocytes, Smooth Muscle; Rabbits; Signal Transduction; Sphingolipids; Sphingomyelin Phosphodiesterase; Sphingomyelins; Sphingosine; trans-Golgi Network; Tumor Necrosis Factor-alpha

2007