Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.23 (MMP)
 4,246 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pyrogallol (PG) as a polyphenol compound induces apoptosis in several types of cells. Here, we investigated the effects of MAPK inhibitors on PG-treated calf pulmonary artery endothelial cells (CPAEC) in relation to cell death, ROS and GSH. PG inhibited the growth of CPAEC and also induced cell death, which was accompanied by the loss of mitochondrial membrane potential (MMP; DeltaPsi(m)). PG decreased the ROS level and increased the GSH depleted cell number in CPAEC. JNK inhibitor intensified the growth inhibition by PG whereas p38 inhibitor attenuated the growth inhibition. While MEK and p38 inhibitors decreased CPAEC death by PG, JNK inhibitor increased. None of the MAPK inhibitors significantly increased ROS level in PG-treated CPAEC. JNK inhibitor increased GSH depleted cell number in PG-treated CPAEC whereas p38 inhibitor decreased the number. MAPK inhibitors differently affected cell growth, death, ROS and GSH levels in control CPACE. In conclusion, PG induced apoptosis via the loss of MMP (DeltaPsi(m)) in CPAEC, which is accompanied by GSH depletion. JNK and p38 inhibitors increased and decreased apoptosis in PG-treated CPAEC, respectively, which were correlated with GSH depletion.
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PMID:JNK and p38 inhibitors increase and decrease apoptosis, respectively, in pyrogallol-treated calf pulmonary arterial endothelial cells. 1978 7

The earthworm, which has stasis removal and wound-healing functions, is a widely used Chinese herbal medicine in China. Schwann cell migration is critical for the regeneration of injured nerves. Schwann cells provide an essentially supportive activity for neuron regeneration. However, the molecular migration mechanisms induced by earthworms in Schwann cells remain unclear. Here, we investigate the roles of MAPK (ERK1/2, JNK and p38) pathways for earthworm-induced matrix-degrading proteolytic enzyme (PAs and MMP2/9) production in Schwann cells. Moreover, earthworm induced phosphorylation of ERK1/2 and p38, but not JNK, activate the downstream signaling expression of PAs and MMPs in a time-dependent manner. Earthworm-stimulated ERK1/2 and p38 phosphorylation was attenuated by pretreatment with U0126 and SB203580, resulting in migration and uPA-related signal pathway inhibition. The results were confirmed using small interfering ERK1/2 and p38 RNA. These results demonstrated that earthworms can stimulate Schwann cell migration and up-regulate PAs and MMP2/9 expression mediated through the MAPK pathways, ERK1/2 and p38. Taken together, our data suggests the MAPKs (ERK1/2, p38)-, PAs (uPA, tPA)-, MMP (MMP2, MMP9) signaling pathway of Schwann cells regulated by earthworms might play a major role in Schwann cell migration and nerve regeneration.
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PMID:Schwann Cell Migration Induced by Earthworm Extract via Activation of PAs and MMP2/9 Mediated through ERK1/2 and p38. 1980 45

Pyrogallol (PG) as a polyphenol compound can generate superoxide anion (O(2)(-)). Here, we investigated the effects of PG and/or MAPK inhibitors on Calu-6 lung cells in relation to cell growth, cell death, reactive oxygen species (ROS) and GSH levels. PG inhibited the growth of Calu-6 cells and induced apoptosis, which was accompanied by the loss of mitochondrial membrane potential (MMP; DeltaPsi(m)). While general ROS were decreased in PG-treated Calu-6 cells at 72h, intracellular O(2)(-) level including mitochondrial O(2)(-) was increased. PG also increased GSH depleted cell number in Calu-6 cells. MEK inhibitor slightly prevented cell growth inhibition, cell death and GSH depletion by PG. JNK inhibitor did not affect cell growth, cell death, MMP (DeltaPsi(m)) loss, ROS level and GSH deletion in PG-treated Calu-6 cells but p38 inhibitor mildly enhanced MMP (DeltaPsi(m)) loss, O(2)(-) level and GSH depletion in these cells. Conclusively, MEK inhibitor slightly prevented growth inhibition and death in PG-treated Calu-6 cells. Growth inhibition and death in Calu-6 cells by PG and/or MAPK inhibitors were partially related to O(2)(-) level and GSH content changes.
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PMID:The effects of MAPK inhibitors on pyrogallol-treated Calu-6 lung cancer cells in relation to cell growth, reactive oxygen species and glutathione. 1983 63

MG132 as a proteasome inhibitor can induce apoptotic cell death through formation of reactive oxygen species (ROS). In this study, we investigated the effects of MAPK (MEK, JNK or p38) inhibitors on MG132-induced HeLa cell death in relation to ROS and glutathione (GSH). MG132-induced cell growth inhibition and apoptosis in HeLa cells, which was accompanied by the loss of mitochondrial membrane potential (MMP; DeltaPsi(m)). MG132 increased ROS level including O(2)(*-) and GSH depleted cell number in HeLa cells. All the MAPK inhibitors slightly enhanced the cell growth inhibition but did not intensify apoptosis in MG132-treated HeLa cells. Each MAPK inhibitor differentially changed the levels of ROS and GSH content in MG132-treated cells. In conclusion, MAPK inhibitors partially influence apoptosis, ROS and GSH levels in MG132-treated HeLa cells.
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PMID:The effects of MAPK inhibitors on a proteasome inhibitor, MG132-induced HeLa cell death in relation to reactive oxygen species and glutathione. 1985 51

Gastrin is a gastrointestinal peptide hormone, secreted by the gastric G cells and can exist as a fully processed amidated form (G17) or as unprocessed forms. All forms of gastrin possess trophic properties towards the gastrointestinal mucosa. An understanding of the signaling pathways involved is important to design therapeutic approaches to target gastrin-mediated cellular events. The studies described here were designed to identify the signaling pathways by which amidated gastrin (G17) mediates cancer cell migration. These studies indicated a time- and dose-dependent increase in gastric cancer cell migration after G17 stimulation, involving cholecystokinin 2 receptor. G17-induced migration was preceded by activation of MAPK pathways and was antagonized after pretreatment with SP600125, a pharmacological inhibitor of c-Jun-NH(2)-terminal kinase (JNK) pathway. Knockdown of endogenous JNK1 expression via small interference RNA (JNK1-siRNA) inhibited G17-induced phosphorylation of c-Jun and migration, and overexpression of wild-type JNK1 or constitutive active JNK1 promoted G17-induced migration. Studies designed to identify the MAPK kinase kinase member mediating JNK activation indicated the involvement of mixed lineage kinase-3 (MLK3), which was transiently activated upon G17 treatment. Inhibition of MLK3 pathway via a pan-MLK inhibitor or knockdown of MLK3 expression by MLK3-siRNA antagonized G17-induced migration. Incubation with G17 also resulted in an induction of matrix metalloproteinase 7 promoter activity, which is known to mediate migration and invasion pathways in cancer cells. Modulation of MLK3, JNK1, and c-Jun pathways modulated G17-induced matrix metalloproteinase 7 promoter activation. These studies indicate that the MLK3/JNK1 axis mediates G17-induced gastric cancer cell migration, which can be targeted for designing novel therapeutic strategies for treating gastric malignancies.
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PMID:Mixed lineage kinase-3/JNK1 axis promotes migration of human gastric cancer cells following gastrin stimulation. 2015 Jan 85

Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has recently been shown to possess antitumor activity in various cancer cells. However, the effects of DHA in preventing the invasion of cancer cells have not been studied. In the present study, we investigated the inhibitory effects of DHA on tumor invasion and migration and the possible mechanisms involved using human fibrosarcoma HT-1080 cells. DHA reduced PMA-induced activation of MMP-9 and MMP-2 and further inhibited cell invasion and migration. DHA suppressed PMA-enhanced expression of MMP-9 protein, mRNA, and transcriptional activity through suppressing NF-kappaB and AP-1 activation without changing the level of tissue inhibitor of metalloproteinase (TIMP)-1. DHA also reduced PMA-enhanced MMP-2 expression by suppressing membrane-type 1 MMP (MT1-MMP), but did not alter TIMP-2 levels. DHA-inhibited PMA-induced NF-kappaB and c-Jun nuclear translocation, which are upstream of PMA-induced MMP-9 expression and invasion. Furthermore, DHA strongly repressed the PMA-induced phosphorylation of Raf/ERK and JNK, which are dependent on the PKCalpha pathway. In conclusion, we demonstrated that the anti-invasive effects of DHA may occur through inhibition of PKCalpha/Raf/ERK and JNK phosphorylation and reduction of NF-kappaB and AP-1 activation, leading to down-regulation of MMP-9 expression. The data presented show that DHA is an effective anti-metastatic agent that functions by down-regulating MMP-9 gene expression.
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PMID:Suppression of PMA-induced tumor cell invasion by dihydroartemisinin via inhibition of PKCalpha/Raf/MAPKs and NF-kappaB/AP-1-dependent mechanisms. 2015 19

Pyrogallol (PG) induces apoptosis in several types of cells mediated by superoxide anion (O(2*-)). Here, we investigated the effects of PG and/or MAPK (MEK, JNK, and p38) inhibitors on the changes in cell growth, cell death, reactive oxygen species (ROS), and GSH levels in As4.1 juxtaglomerular (JG) cells. PG inhibited the growth of As4.1 cells. It also induced apoptosis and the loss of mitochondrial membrane potential (MMP; DeltaPsi(m)) and increased the level of p53 protein. Intracellular O2(*-) level was increased in PG-treated As4.1 cells. PG also increased the number of GSH deleted cells in As4.1 cells. All the MAPK inhibitors significantly attenuated the growth inhibition and death mediated by PG. They decreased the levels of p53 protein and MMP (DeltaPsi(m)) loss in PG-treated As4.1 cells. They also reduced O2(*-) level and GSH-depleted cell number in these cells. In conclusion, MAPK inhibitors attenuated As4.1 cell growth inhibition and death mediated by PG treatment. The changes in O2(*-) and GSH levels by PG and/or MAPK inhibitors appeared to affect the growth and death of As4.1 cells.
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PMID:Pyrogallol-induced As4.1 juxtaglomerular cell death is attenuated by MAPK inhibitors via preventing GSH depletion. 2019 Dec 65

MG132, as a proteasome inhibitor, can induce apoptotic cell death through formation of reactive oxygen species (ROS). In this study, we investigated the effects of MAPK (MEK, JNK, and p38) inhibitors on MG132-treated A549 lung cancer cells in relation to cell growth, cell death, ROS, and glutathione (GSH) levels. Treatment with 10 microM MG132 inhibited the growth of A549 cells at 24 h. MG132 also induced apoptosis, which was accompanied by the loss of mitochondrial membrane potential (MMP; deltapsi(m)). ROS were not increased in MG132-treated A549 cells. MG132 increased GSH-depleted cell numbers and decreased GSH levels. MEK and JNK inhibitors did not strongly affect cell growth, cell death, ROS, and GSH levels in MG132-treated A549 cells. In contrast, p38 inhibitor reduced cell growth inhibition, apoptosis, and MMP (deltapsi(m)) loss by MG132. However, p38 inhibitor did not change ROS level and GSH content. In conclusion, MG132 inhibited the growth of A549 cells via apoptosis without formation of ROS. Treatment with p38 inhibitor rescued some cells from MG132-induced apotposis, which was not affected by ROS and GSH level changes.
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PMID:The attenuation of MG132, a proteasome inhibitor, induced A549 lung cancer cell death by p38 inhibitor in ROS-independent manner. 2037 32

MG132, as a proteasome inhibitor, has been shown to induce apoptotic cell death through the formation of reactive oxygen species (ROS). In this study, we investigated the effects of MG132 and/or MAPK inhibitors on As4.1 juxtaglomerular cells in relation to cell growth, cell death, ROS, and glutathione (GSH) levels. MG132 inhibited the growth of As4.1 cells and induced cell death, accompanied by the loss of mitochondrial membrane potential (MMP; DeltaPsi(m)) and activation of caspase-3 and -8. MG132 increased ROS levels, and GSH depleted cell numbers. The MEK inhibitor slightly reduced cell growth and caspase-3 activity in MG132-treated As4.1 cells and mildly increased MMP (DeltaPsi(m)) loss and O(2)(*-) level. However, it did not increase apoptosis and GSH depletion. The JNK inhibitor did not strongly influence cell growth, cell death, and GSH depletion by MG132, but increased caspase-3 activity, MMP (DeltaPsi(m)) loss, and O(2)(*-) level. Treatment with the p38 inhibitor magnified cell-growth inhibition and apoptosis by MG132. This agent also strongly increased caspase-8 activity, MMP (DeltaPsi(m)) loss, O(2)(*-) level, and GSH depletion. Conclusively, the p38 inhibitor strongly intensified cell death in MG132-treated As4.1 cells. The changes of GSH content by MG132 and/or MAPK inhibitors were closely related to the death of As4.1 cells.
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PMID:Treatment with p38 inhibitor intensifies the death of MG132-treated As4.1 juxtaglomerular cells via the enhancement of GSH depletion. 2054

Propofol (2,6-diisopropylphenol), one of the most commonly used intravenous anaesthetic agents during cancer resection surgery, has been reported to have the ability of influencing the invasion of human cancer cells. In the present study, using the human colon carcinoma cell line LOVO, we demonstrated that propofol stimulation significantly decreased the expression of MMP-2 and -9 and subsequently decreased the invasive activity of the cancer cells. Because MAPK signaling is one of the key regulators of MMP expression, we further evaluated MAPK signaling after stimulation with propofol. It was found that propofol stimulation inhibited the phosphorylation of MAPKs, including ERK1/2, JNK, and p38. Deactivation of ERK1/2 phosphorylation was sustained for up to 12h, while deactivation of phosphorylation of JNK and p38 returned to the endogenous level by 30 min. It was noteworthy that the ras/raf/MEK/ERK pathway inhibitor PD98059 attenuated the down-regulation of propofol-induced MMP-9 expression of LOVO cells. We also demonstrated that the propofol-induced decrease in invasive ability via ERK1/2 down-regulation was mediated mainly through the GABA-A receptor. These results indicate that propofol stimulation inhibits cancer cell invasion and that the effect is partly due to ERK1/2-dependent down-regulation of MMPs.
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PMID:GABA-receptor agonist, propofol inhibits invasion of colon carcinoma cells. 2088 81


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