Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In rat pheochromocytoma PC12 cells, NGF induces neuronal differentiation. Upon stimulation with NGF, Ras is activated to a GTP-bound form, and the activated Ras can induce neuronal differentiation. Recently, we and others observed that epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) can also activate Ras in PC12 cells. This is puzzling since previous reports indicated that EGF stimulates proliferation rather than differentiation in PC12 cells. In this paper, we re-examined the biological effect of EGF and TGF-alpha, and found that these factors can also induce neuronal differentiation under particular culture conditions. Not only the outgrowth of long neurites, but the induction of neurofilament proteins and the metalloprotease transin was also observed in the EGF- and TGF-alpha-stimulated cells. These data clearly indicate that in addition to NGF, EGF and TGF-alpha can also induce the differentiation of PC12 cells under particular conditions.
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PMID:Epidermal growth factor and transforming growth factor-alpha can induce neuronal differentiation of rat pheochromocytoma PC12 cells under particular culture conditions. 842 11

Human skin is exposed daily to solar ultraviolet (UV) radiation. UV induces the matrix metalloproteinases collagenase, 92-kD gelatinase, and stromelysin, which degrade skin connective tissue and may contribute to premature skin aging (photoaging). Pretreatment of skin with all-trans retinoic acid (tRA) inhibits UV induction of matrix metalloproteinases. We investigated upstream signal transduction pathways and the mechanism of tRA inhibition of UV induction of matrix metalloproteinases in human skin in vivo. Exposure of human skin in vivo to low doses of UV activated EGF receptors, the GTP-binding regulatory protein p21Ras, and stimulated mitogen-activated protein (MAP) kinases, extracellular signal-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38. Both JNK and p38 phosphorylated, and thereby activated transcription factors c-Jun and activating transcription factor 2 (ATF-2), which bound to the c-Jun promoter and upregulated c-Jun gene expression. Elevated c-Jun, in association with constitutively expressed c-Fos, formed increased levels of transcription factor activator protein (AP) 1, which is required for transcription of matrix metalloproteinases. Pretreatment of human skin with tRA inhibited UV induction of c-Jun protein and, consequently, AP-1. c-Jun protein inhibition occurred via a posttranscriptional mechanism, since tRA did not inhibit UV induction of c-Jun mRNA. These data demonstrate, for the first time, activation of MAP kinase pathways in humans in vivo, and reveal a novel posttranscriptional mechanism by which tRA antagonizes UV activation of AP-1 by inhibiting c-Jun protein induction. Inhibition of c-Jun induction likely contributes to the previously reported prevention by tRA of UV induction of AP-1-regulated matrix-degrading metalloproteinases in human skin.
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PMID:Retinoic acid inhibits induction of c-Jun protein by ultraviolet radiation that occurs subsequent to activation of mitogen-activated protein kinase pathways in human skin in vivo. 950 86

Chronic exposure of solar ultraviolet (UV) light to human skin results in photoaging. UV-induced oxidative damage and induction of matrix metalloproteinases (MMP) have been implicated in this process. Because polyphenols from green tea (GTP) prevent other cutaneous adverse effects of UV radiation we hypothesized that UV irradiation-induced oxidative damage and induction of MMP might be prevented in vivo in mouse skin by oral administration of GTP. GTP was administered in drinking water (0.2%, wt/vol) to SKH-1 hairless mice, which were then exposed to multiple doses of UVB (90 mJ per cm2, for 2 mo on alternate days) following in vivo photoaging animal protocol. Treatment of GTP resulted in inhibition of UVB-induced protein oxidation in vivo in mouse skin, a hallmark of photoaging, when analyzed biochemically, by immunoblotting, and immunohistochemistry. GTP treatment also inhibited UVB-induced protein oxidation in vitro in human skin fibroblast HS68 cells, which supports in vivo observations. Moreover, oral administration of GTP also resulted in inhibition of UVB-induced expression of matrix degrading MMP, such as MMP-2 (67%), MMP-3 (63%), MMP-7 (62%), and MMP-9 (60%) in hairless mouse skin. These data suggest that GTP as a dietary supplement could be useful to attenuate solar UVB light-induced premature skin aging.
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PMID:Green tea polyphenols prevent ultraviolet light-induced oxidative damage and matrix metalloproteinases expression in mouse skin. 1517 40

1.--Thrombin is activated during gingival tissue injury and inflammation. Thrombin (platelet)-rich plasma has been used for periodontal regeneration with success. Thrombin and other bacterial proteases also affect the functions of adjacent periodontal cells via stimulation of protease-activated receptors (PARs). 2.--We noted that thrombin (0.1-2 U ml(-1)), human, and frog PAR-1 agonist peptide (20-240 microM) induced the gingival fibroblast (GF)-populated collagen gel contraction within 2 h of exposure. However, PAR-2, PAR-3, and PAR-4 agonist peptide (20-240 microM) showed little effect on collagen gel contraction. U73122 (phospholipase C inhibitor) and 2-APB (IP3 antagonist) were effective in inhibition of GF contraction. 3.--Thrombin-induced GF contraction was inhibited by 5 mM EGTA (an extracellular calcium chelator) and verapamil (an L-type calcium channel blocker). In addition, W7 (10 and 25 microM, a calcium/calmodulin (CaM) inhibitor), ML-7 (50 microM, myosin light chain kinase (MLCK) inhibitor), and HA1077 (100 microM, Rho kinase inhibitor) completely inhibited the thrombin-induced collagen gel contraction. Thrombin also induced the phosphorylation of ERK1/ERK2 and elevated the Rho-GTP levels in GF. 4.--However, U0126 only partially inhibited the thrombin-induced GF contraction. Similarly, wortmannin (100 nM), LY294002 (20 microM) (two PI3K inhibitor) and genistein also showed partial inhibition. Moreover, NAC was not able to suppress the GF contraction, as supported by the slight decrease in reactive oxygen species production in GF by thrombin. 5.--Thrombin also stimulated metalloproteinase-2 (MMP-2) and MMP-3 production in GF. But addition of GM6001 or 1,10-phenanthroline, two MMP inhibitors, could not inhibit the thrombin-induced GF contraction. 6.--These results indicate that thrombin is crucial in the periodontal inflammation and wound healing by promoting GF contraction. This event is mainly mediated via PAR-1 activation, PLC activation, extracellular calcium influx via L-type calcium channel, and the calcium/CaM-MLCK and Rho kinase activation pathway.
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PMID:Signaling mechanism of thrombin-induced gingival fibroblast-populated collagen gel contraction. 1629 51