AP-1 (Fra-1/c-Jun)-mediated Induction of Expression of Matrix Metalloproteinase-2 Is Required for 15(S)-Hydroxyeicosatetraenoic Acid-induced Angiogenesis
Abstract:To understand the involvement of matrix metalloproteinases (MMPs) in 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE)-induced angiogenesis, we have studied the role of MMP-2. 15(S)-HETE induced MMP-2 expression and activity in a timedependent manner in human dermal microvascular endothelial cells (HDMVECs). Inhibition of MMP-2 activity or depletion of its levels attenuated 15(S)-Angiogenesis has been implicated in the pathogenesis of cancer, diabetic retinopathy, and atherosclerosis (1). On the other hand, a th… Show more
“…15(S)-HETE stimulated the tyrosine phosphorylation of ␣Pix in a timedependent manner ( Figure 4A). Because our previous studies showed that 15(S)-HETE stimulates Src, 24,25 we asked the question whether this non-receptor tyrosine kinase plays a role in 15(S)-HETE-induced ␣Pix phosphorylation. Adenovirus-mediated transduction of dominant negative Src completely blocked 15(S)-HETE-induced ␣Pix phosphorylation ( Figure 4B).…”
“…25 The treatment conditions were the same as those applied in migration assay. Vehicle or 15(S)-HETE, at the indicated concentrations, were added to the appropriate well and the cells were incubated at 37°C for 6 hours.…”
Section: Tube Formationmentioning
confidence: 99%
“…23,25 To understand the mechanisms by which 15(S)-HETE activates Rac1 in these cells, we have studied the role of HMG-CoA reductase and RhoGEFs as these molecules play an important role in RhoGTPase farnesylation and GDP/GTP exchange, respectively. [32][33][34][35] In agreement with our previous observations, 15(S)-HETE (0.1M) stimulated Rac1 in a time-dependent manner ( Figure 1A).…”
“…25 Vehicle or 15(S)-HETE were added to the lower chamber at the indicated concentrations. Both the upper and lower chambers contained medium 131.…”
Section: Cell Migrationmentioning
confidence: 99%
“…25 Mice were anesthetized with intraperitoneal injection of ketamine (100 mg/kg) and xylazine (8 mg/kg). Aseptic surgery was performed to ligate the left common femoral artery as follows.…”
“…15(S)-HETE stimulated the tyrosine phosphorylation of ␣Pix in a timedependent manner ( Figure 4A). Because our previous studies showed that 15(S)-HETE stimulates Src, 24,25 we asked the question whether this non-receptor tyrosine kinase plays a role in 15(S)-HETE-induced ␣Pix phosphorylation. Adenovirus-mediated transduction of dominant negative Src completely blocked 15(S)-HETE-induced ␣Pix phosphorylation ( Figure 4B).…”
“…25 The treatment conditions were the same as those applied in migration assay. Vehicle or 15(S)-HETE, at the indicated concentrations, were added to the appropriate well and the cells were incubated at 37°C for 6 hours.…”
Section: Tube Formationmentioning
confidence: 99%
“…23,25 To understand the mechanisms by which 15(S)-HETE activates Rac1 in these cells, we have studied the role of HMG-CoA reductase and RhoGEFs as these molecules play an important role in RhoGTPase farnesylation and GDP/GTP exchange, respectively. [32][33][34][35] In agreement with our previous observations, 15(S)-HETE (0.1M) stimulated Rac1 in a time-dependent manner ( Figure 1A).…”
“…25 Vehicle or 15(S)-HETE were added to the lower chamber at the indicated concentrations. Both the upper and lower chambers contained medium 131.…”
Section: Cell Migrationmentioning
confidence: 99%
“…25 Mice were anesthetized with intraperitoneal injection of ketamine (100 mg/kg) and xylazine (8 mg/kg). Aseptic surgery was performed to ligate the left common femoral artery as follows.…”
Our data indicate that MMP-2 and MMP-9 downregulation in gallic acid treated K562 cells are mediated through suppression of JNK1-mediated c-Jun/ATF-2 and Akt/ERK-mediated c-Jun/c-Fos pathways, respectively.
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