No abstract available.
Humans* ; Metalloproteases ; Prostate* ; Prostatic Neoplasms

Intimal hyperplasia is a feature of the normal adaptive response of vessels to hemodynamic stresses, as well as being a characteristic of vessel injuries that are healing. Intimal hyperplasia in the region of endarterectomy, balloon angioplasty and vascular bypass graft anastomosis is a major cause of the long-term failure of vascular reconstruction. The underlying causes of intimal hyperplasia are proliferation and migration of vascular smooth muscle cells, and this is all provoked by injury, inflammation and mechanical stretch. This review discusses both the final common pathways that lead to smooth muscle cell migration and proliferation and their patho-physiological triggers. In this review, we have critically evaluated and summarized the literature to understand and interlink the numerous established and emerging factors that play key roles in the development of intimal hyperplasia.
Angioplasty, Balloon ; Endarterectomy ; Glycosaminoglycans ; Hemodynamics ; Hyperplasia ; Inflammation ; Metalloproteases ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle ; Transplants

Genipin, an aglycone derived from geniposide found in Gardenia jasminoides, is known to be an excellent natural cross-linker, strong apoptosis inducer, and antiviral agent. Although evidence suggests antiviral activity of genipin in several in vitro viral infection systems, there have been few literatures which review antitumor effects of genipin in a variety of in vitro/in vivo models of cancers yet. In this review, we present some of the latest findings in the studies of genipin focusing on antitumor effects and its mechanisms. In brief, genipin inhibits mitochondrial uncoupling protein 2 to increase accumulation of reactive oxygen species, leading to ROS/c-Jun N-terminal kinase-dependent apoptosis of cancer cells. Genipin also increase tissue inhibitors of metalloproteases (MMP), resulting to decrease activities of MMP-2 which plays a key role in metastasis of cancers. Genipin has shown a biphasic effects on cell death and survival in cancer cells as many other plant-derived phytochemicals do. Finally we discuss the potential of genipin as a promosing novel antitumor agent which could be applicable to chemotherapy and/or chemoprevention for cancers.
Apoptosis ; Cell Death ; Chemoprevention ; Drug Therapy ; Gardenia ; In Vitro Techniques ; Metalloproteases ; Neoplasm Metastasis ; Phytochemicals ; Reactive Oxygen Species

BACKGROUND: One of the most important steps in neoplastic progression is represented by invasion of surrounding normal tissues by neoplastic cells. Enzymes such as the metalloproteinases(MMPs) are thought to be involved in the process of destruction of basement membranes and stromal invasion by tumor cells. OBJECTIVE: We investigated the expression patterns of MMP-2 and MMP-9 in acquired and congenital melanocytic nevi, and malignant melanoma by immunohistochemical technique. METHOD: Formalin-fixed and paraffin-embedded tissues from 4 junctional nevi, 4 compound nevi, 5 intradermal nevi, 6 congenital melanocytic nevi, and 6 malignant melanomas were immunolabelled with monoclonal antibodies directed against MMP-2 and MMP-9. RESULT: The benign melanocytic nevi showed negative or low expression for MMP-2 and MMP-9 with the exception of positive staining in involuting neuroid intradermal nevus, and the expression of MMP-9 was detected in 3 cases of congenital melanocytic nevi. The malignant melanoma exhibited high expression of MMP-2 with variable intensity of reactivity in different areas of the tumors and MMP-9 was found to be focally expressed by the tumor cells in intraepidermal and dermoepidermal junction. These findings suggest that the expression of MMP-2 and MMP-9 may be related to tumorigenesis of melanocytic tumors and MMP-9 may be involved in the early stage of tumor progression.
Antibodies, Monoclonal ; Basement Membrane ; Carcinogenesis ; Melanoma* ; Metalloproteases* ; Nevus ; Nevus, Intradermal ; Nevus, Pigmented*

Proteomics is a fast-growing discipline that aims at systematic identification, quantification of proteins and their post-translational modifications in cells. Mass spectrometry-based shotgun proteomics technology is currently one of the mainstream methods for proteomics research. With this method, proteins need to be digested to peptides by site-specific proteases before they can be detected with mass spectrometry. Therefore, site-specific proteases played key roles in this process and so far, a variety of specific proteases have been developed and used in proteomics study. Particularly, the identification, characterization and development of proteases that cleave at the N-termini of corresponding amino acid residues, which are just mirrors to those of typical C-termini proteases, provide novel tools for proteomics analysis. In this review, we summarized the proprieties of LysargiNase, a most recently identified mirror trypsin, and its applications in proteomics research to promote its more widespread usage.
Mass Spectrometry ; Metalloproteases ; chemistry ; metabolism ; Protein Processing, Post-Translational ; Proteomics ; Trypsin ; chemistry

OBJECTIVE: Tissue inhibitors of metalloproteinases (TIMPs) play a key role in maintaining homeostasis of the extracellular matrix (ECM) by controlling matrix metalloproteinases (MMPs). In addition to their role in regulating MMPs, TIMPs have also been shown to have pluripotential effects on cell growth, apoptosis and differentiation. The aim of this study was to examine TIMP-2 level in serous ovarian tumor tissues and to understand further the role of TIMP-2 protein in ovarian tumorigenesis. METHODS: Expression of TIMP-2 was assessed by immunohistochemistry in a total of 57 ovarian specimens including five normal ovaries, 12 benign serous cystadenomas, 20 serous borderline tumors and 20 serous carcinomas. RESULTS: The present study found that TIMP-2 immunostaining was significantly more frequent in serous carcinomas, mainly in tumor epithelium, compared with cells of the other tissues studied. CONCLUSION: TIMP-2 in serous ovarian carcinoma may function to favor tumor growth in serous ovarian tumorigenesis. Additional research is now needed to elucidate further the role of TIMP-2 in the biological behavior of ovarian serous tumors.
Apoptosis ; Carcinogenesis ; Cystadenoma, Serous ; Epithelium ; Extracellular Matrix ; Female ; Homeostasis ; Immunohistochemistry ; Matrix Metalloproteinases ; Metalloproteases ; Ovarian Neoplasms ; Ovary ; Tissue Inhibitor of Metalloproteinase-2

OBJECTIVETo investigate the effects of overdosed fluoride on the expression of MMP-20 and TIMP-2 in rat incisor.

METHODS20 Wistar rats were randomly divided into experiment group and control group. The distilled water was given in control group. 100 mg/L fluoride- was given in experiment group. After 8 weeks treatment, the rats were killed. Immunohistochemical staining was used to observe the expression of MMP-20 and TIMP-2 in rat incisors.

RESULTSImmunohistochemical results demonstrated the presence of MMP-20 and TIMP-2 protein in ameloblasts, odontoblasts, stratum intermedium and the stellate reticulum of rat incisor. The imagination analysis results showed that the expression of MMP-20 was reduesed in experiment group (P<0.01), and the expression of TIMP-2 had no significant difference (P>0.05).

CONCLUSIONThe overdosed fluoride inhibits the secretion of MMP-20 and leads to the disturbed balance between MMP-20, TIMP-2 in rat incisor, which leads to the delay of the amelogenin removal and the enamel demineralization.

Ameloblasts ; Animals ; Dental Enamel ; Fluorides ; Fluorosis, Dental ; Incisor ; Metalloproteases ; Phosphates ; Rats ; Rats, Wistar ; Tissue Inhibitor of Metalloproteinase-2

BACKGROUND: Mucus hypersecretion in the patients with airway diseases represents poor prognosis as well as discomfort. However, there is no known therapy for its effective control. One important component of mucus is mucin, a glycosylated protein, which endows mucus with viscosity. We studied whether a proteinase has a role in mucin secretion and if so, which. METHODS: (1) Inhibition of mucin secretion Group-specific proteinase inhibitors were tested to evaluate whether a proteinase belonging to a group of proteinases plays a role in mucin secretion. Phenylmethylsulfonyl fluoride(PMSF, a serine proteinase inhibitor), E-64(a cysteine proteinase inhibitor), Pepstatin(an aspartic proteinase inhibitor) and 1, 10-Phenanthroline(a metalloproteinase inhibitor) were treated into the Calu-3 cell line for 24 hours. The enzyme linked immunoabsorbant assay(ELISA) for MUC5AC was performed to evaluate the amount of mucin secretion and to compare with a control. (2) Stimulation of mucin secretion Matrix metalloproteinase-9(MMP-9), MMP-12 and TACE(TNF-alpha converting enzyme), which are known to be related with airway diseases, were used to be treated into Calu-3 for 24 hours. ELISA for MUC5AC was performed to evaluate the amount of mucin secretion and to compare with the controls. RESULTS: (1) PMSF(10(-4)M), E-64(10(-4)M), Pepstatin(10(-6)M) and 1, 10-Phenanthroline(10(-4)M) reduced the MUC5AC secretion by 1 +/- 4.9%(mean +/- standard deviation; P=1.0 compared with the control), -6 +/- 3.9%(P=0.34), -13 +/- 9.7%(P=0.34) and 41 +/- 8.2%(P=0.03), respectively. (2) The amounts of MUC5AC secretion stimulated by MMP-9(250ng/ml), MMP-12(100ng/ml) and TACE(200ng/ml) were 103 +/- 6%(P=0.39), 102 +/- 8%(P=1.0) and 107 +/- 13%(P=0.39), respectively, compared with the controls. CONCLUSION: Metalloproteinase(s) is (are) suggested to play a role in mucin secretion. It appears that metalloproteinases, other than MMP-9, MMP-12 or TACE, affect the mucin secretion in this in vitro model.
Cell Line ; Cysteine Proteases ; Enzyme-Linked Immunosorbent Assay ; Humans ; Metalloproteases ; Mucins* ; Mucus ; Peptide Hydrolases ; Prognosis ; Serine Proteases ; Viscosity

Curtobacterium luteum, a gram-positive psychrotrophic bacterium, secreting an extracellular protease was isolated from the soil of Gangotri glacier, Western Himalaya. The maximum enzyme production was achieved when isolate was grown in a pH-neutral medium containing skim milk at 15 degrees C over 120 hour. The metal ions such as Zn2+ and Cr2+ enhanced enzyme production. The specific activity of purified enzyme was 8090 u/mg after 34.1 fold purification. The 115 kD enzyme was a metalloprotease (activity inhibited by EDTA and EGTA) and showed maximum activity at 20 degrres C and pH 7. The enzyme was active over a broad pH range and retained 84% of its original activity between pH 6-8. There was no loss in enzyme activity when exposed for 3 hours at 4 degrees C-20 degrees C. However, lost 65% of activity at 30 degrees C, and was almost inactivated at 50 dgrees C, but was resistant to repeated freezing and thawing. The enzyme activity was stimulated by manganese ions; however, it was inactivated by copper ions.
Actinomycetales ; enzymology ; growth & development ; Cold Temperature ; Culture Media ; Enzyme Stability ; Hydrogen-Ion Concentration ; Metalloproteases ; isolation & purification ; metabolism ; Soil Microbiology

This study investigated the effects of inorganic sulfur on metastasis in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured in the absence or presence of various concentrations (12.5, 25, or 50 micromol/L) of inorganic sulfur. Cell motility, invasion, and the activity and mRNA expression of matrix metalloproteases (MMPs) were examined. Numbers of viable MDA-MB-231 cells did not differ by inorganic sulfur treatment from 0 to 50 micromol/L within 48 h. Inorganic sulfur significantly decreased cell motility and invasion in the MDA-MB-231 cells in a dose-dependent manner (P < 0.05), as determined using a Boyden chamber assay and a Matrigel chamber. The activities of MMP-2 and MMP-9 were significantly reduced by inorganic sulfur in a dose-dependent manner (P < 0.05). The inorganic sulfur also significantly inhibited MMP-2 and MMP-9 expression in the cells (P < 0.05). These data suggest that inorganic sulfur can suppress cancer cell motility and invasion by inhibiting MMP-2 and MMP-9 activity and gene expression in MDA-MB-231 cells.
Breast ; Breast Neoplasms ; Cell Movement ; Collagen ; Drug Combinations ; Gene Expression ; Humans ; Laminin ; Metalloproteases ; Neoplasm Metastasis ; Proteoglycans ; RNA, Messenger ; Sulfur