scholarly journals Systematic Analysis of Protease Gene Expression in the Rhesus Macaque Ovulatory Follicle: Metalloproteinase Involvement in Follicle Rupture

Endocrinology ◽  
2011 ◽  
Vol 152 (10) ◽  
pp. 3963-3974 ◽  
Author(s):  
Marina C. Peluffo ◽  
Melinda J. Murphy ◽  
Serena Talcott Baughman ◽  
Richard L. Stouffer ◽  
Jon D. Hennebold
Keyword(s):  
Rhesus Macaques ◽  
Cathepsin L ◽  
Protease Gene ◽  
Mrna Levels ◽  
Systematic Analysis ◽  
Ovulatory Follicle ◽  
Follicle Rupture ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
A Disintegrin And Metalloproteinase

Protease genes were identified that exhibited increased mRNA levels before and immediately after rupture of the naturally selected, dominant follicle of rhesus macaques at specific intervals after an ovulatory stimulus. Quantitative real-time PCR validation revealed increased mRNA levels for matrix metalloproteinase (MMP1, MMP9, MMP10, and MMP19) and a disintegrin and metalloproteinase with thrombospondin-like repeats (ADAMTS1, ADAMTS4, ADAMTS9, and ADAMTS15) family members, the cysteine protease cathepsin L (CTSL), the serine protease urokinase-type plasminogen activator (PLAU), and the aspartic acid protease pepsinogen 5 (PGA5). With the exception of MMP9, ADAMTS1, and PGA5, mRNA levels for all other up-regulated proteases increased significantly (P < 0.05) 12 h after an ovulatory human chorionic gonadotropin (hCG) bolus. MMP1, -10, and -19; ADAMTS1, -4, and -9; CTSL; PLAU; and PGA5 also exhibited a secondary increase in mRNA levels in 36-h postovulatory follicles. To further determine metalloproteinase involvement in ovulation, vehicle (n = 4) or metalloproteinase inhibitor (GM6001, 0.5 μg/follicle, n = 8) was injected into the preovulatory follicle at the time of hCG administration. Of the eight GM6001-injected follicles, none displayed typical stigmata indicative of ovulation at 72 h after hCG; whereas all four vehicle-injected follicles ovulated. No significant differences in mean luteal progesterone levels or luteal phase length occurred between the two groups. Subsequent histological analysis revealed that vehicle-injected follicles ruptured, whereas GM6001-injected follicles did not, as evidenced by an intact stroma and trapped oocytes (n = 3). These findings demonstrate metalloproteinases are critical for follicle rupture in primates, and blocking their activity would serve as a novel, nonhormonal means to achieve contraception.

scholarly journals Profile of Matrix-Remodeling Proteinases in Osteoarthritis: Impact of Fibronectin

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 40 ◽  
Author(s):  
Selene Pérez-García ◽  
Mar Carrión ◽  
Irene Gutiérrez-Cañas ◽  
Raúl Villanueva-Romero ◽  
David Castro ◽  
...  
Keyword(s):  
Feedback Loop ◽  
Three Dimensional ◽  
Matrix Remodeling ◽  
Synovial Joint ◽  
Surface Receptors ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Fibronectin Fragments ◽  
Macromolecular Network ◽  
A Disintegrin And Metalloproteinase

The extracellular matrix (ECM) is a complex and specialized three-dimensional macromolecular network, present in nearly all tissues, that also interacts with cell surface receptors on joint resident cells. Changes in the composition and physical properties of the ECM lead to the development of many diseases, including osteoarthritis (OA). OA is a chronic degenerative rheumatic disease characterized by a progressive loss of synovial joint function as a consequence of the degradation of articular cartilage, also associated with alterations in the synovial membrane and subchondral bone. During OA, ECM-degrading enzymes, including urokinase-type plasminogen activator (uPA), matrix metalloproteinases (MMPs), and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs), cleave ECM components, such as fibronectin (Fn), generating fibronectin fragments (Fn-fs) with catabolic properties. In turn, Fn-fs promote activation of these proteinases, establishing a degradative and inflammatory feedback loop. Thus, the aim of this review is to update the contribution of ECM-degrading proteinases to the physiopathology of OA as well as their modulation by Fn-fs.

scholarly journals Activation and proliferation signals in murine macrophages. Biochemical signals controlling the regulation of macrophage urokinase-type plasminogen activator activity by colony-stimulating factors and other agents

Blood ◽  
1991 ◽  
Vol 77 (3) ◽  
pp. 616-627 ◽  
Author(s):  
JA Hamilton ◽  
G Vairo ◽  
KR Knight ◽  
BG Cocks
Keyword(s):  
Plasminogen Activator ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Peritoneal Macrophages ◽  
Mrna Levels ◽  
Hematopoietic Growth Factors ◽  
Murine Bone Marrow ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Biochemical Signals

Abstract Purified hematopoietic growth factors such as colony-stimulating factor- 1 (CSF-1) or macrophage CSF, granulocyte-macrophage CSF, and interleukin-3 or multi-CSF, stimulate the urokinase-type plasminogen activator (u-PA) activity of murine bone marrow-derived macrophages (BMM) and resident peritoneal macrophages. Granulocyte-CSF was inactive. The increases in BMM u-PA activity were inhibited by the glucocorticoid dexamethasone, and by agents that raise intracellular cyclic adenosine monophosphate levels, including prostaglandin E2 and cholera toxin. These changes in u-PA activity were paralleled by corresponding changes in u-PA mRNA levels. Evidence was obtained for protein kinase C and phospholipase C-mediated stimulation of BMM u-PA activity and mRNA levels; however, no evidence was found for an involvement of Na+/H+ exchange or Na+, K(+)-ATPase activity, Ca2+ fluxes, or pertussis toxin-sensitive G proteins. Several findings point to a dissociation between macrophage u-PA expression and DNA synthesis.

scholarly journals Activation and proliferation signals in murine macrophages. Biochemical signals controlling the regulation of macrophage urokinase-type plasminogen activator activity by colony-stimulating factors and other agents

Blood ◽  
1991 ◽  
Vol 77 (3) ◽  
pp. 616-627
Author(s):  
JA Hamilton ◽  
G Vairo ◽  
KR Knight ◽  
BG Cocks
Keyword(s):  
Plasminogen Activator ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Peritoneal Macrophages ◽  
Mrna Levels ◽  
Hematopoietic Growth Factors ◽  
Murine Bone Marrow ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Biochemical Signals

Purified hematopoietic growth factors such as colony-stimulating factor- 1 (CSF-1) or macrophage CSF, granulocyte-macrophage CSF, and interleukin-3 or multi-CSF, stimulate the urokinase-type plasminogen activator (u-PA) activity of murine bone marrow-derived macrophages (BMM) and resident peritoneal macrophages. Granulocyte-CSF was inactive. The increases in BMM u-PA activity were inhibited by the glucocorticoid dexamethasone, and by agents that raise intracellular cyclic adenosine monophosphate levels, including prostaglandin E2 and cholera toxin. These changes in u-PA activity were paralleled by corresponding changes in u-PA mRNA levels. Evidence was obtained for protein kinase C and phospholipase C-mediated stimulation of BMM u-PA activity and mRNA levels; however, no evidence was found for an involvement of Na+/H+ exchange or Na+, K(+)-ATPase activity, Ca2+ fluxes, or pertussis toxin-sensitive G proteins. Several findings point to a dissociation between macrophage u-PA expression and DNA synthesis.

A new genetic approach for studying hormonal regulation of urokinase-type plasminogen activator gene expression in LLC-PK1 cells

1987 ◽  
Vol 7 (12) ◽  
pp. 4535-4541
Author(s):  
P Hofstetter ◽  
Z Kikinis ◽  
M S Altus ◽  
D Pearson ◽  
Y Nagamine
Keyword(s):  
Protein Kinase ◽  
Plasminogen Activator ◽  
Hormonal Regulation ◽  
Regulatory Region ◽  
Regulatory Proteins ◽  
Protein Kinase Activity ◽  
Mrna Levels ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Upa Mrna

In LLC-PK1 cells, a cyclic AMP (cAMP)-elevating peptide hormone, calcitonin, induces urokinase-type plasminogen activator (uPA) gene transcription without concomitant protein synthesis. To understand the molecular mechanism of the uPA gene regulation by cAMP, we developed a system which allows us to obtain mutant cells with modified regulatory proteins. A uPA-gpt hybrid gene was constructed, in which the regulatory region of the uPA gene was linked to a bacterial xanthine-guanine phosphoribosyltransferase gene (gpt), and it was transfected into LLC-PK1 cells. A stably transformed cell line, which expressed gpt only in the presence of calcitonin, was obtained, and then these cells were treated with a chemical mutagen, ethyl methanesulfonate. Cells were screened for constitutive gpt expression and, as mutations in regulatory proteins should affect the two genes at the same time, cells were further screened for an increased basal uPA mRNA level. Several such clones were obtained and none of them had modified cAMP-dependent protein kinase activity, suggesting that mutations were in the post-protein kinase step in the pathway of hormone action. Five clones were fused with the parent LLC-PK1 cells, and all of the fusion cells showed reduced basal uPA mRNA levels, indicating that they were recessive mutants. One clone was analyzed further for sensitivity to calcitonin in the induction of uPA mRNA, and it showed a significantly different dose-response pattern compared with parent cells. These results suggest that the uPA gene is regulated, at least partly, by a negatively regulating factor and that the action of cAMP is linked to this factor.

Effective activation of the proenzyme form of the urokinase-type plasminogen activator (pro-uPA) by the cysteine protease cathepsin L

FEBS Letters ◽  
1992 ◽  
Vol 297 (1-2) ◽  
pp. 112-118 ◽  
Author(s):  
Lothar Goretzki ◽  
Manfred Schmitt ◽  
Karlheinz Mann ◽  
Juan Calvete ◽  
Nicolaus Chucholowski ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Cysteine Protease ◽  
Cathepsin L ◽  
Effective Activation ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator

scholarly journals Gamma interferon enhances macrophage transcription of the tumor necrosis factor/cachectin, interleukin 1, and urokinase genes, which are controlled by short-lived repressors.

1986 ◽  
Vol 164 (6) ◽  
pp. 2113-2118 ◽  
Author(s):  
M A Collart ◽  
D Belin ◽  
J D Vassalli ◽  
S de Kossodo ◽  
P Vassalli
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Peritoneal Macrophages ◽  
Mrna Levels ◽  
Ifn Gamma ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Inhibitor Of Protein Synthesis ◽  
Necrosis Factor

Exposure of mouse resident and thioglycollate-elicited peritoneal macrophages to IFN-gamma leads to a marked increase in the TNF-alpha (tumor necrosis factor/cachectin), IL-1 and u-PA (urokinase-type plasminogen activator) mRNA levels. Nuclear run-on experiments show that IFN-gamma acts by enhancing the transcription of these three genes. Transcription of these three genes is also rapidly and transiently induced by cycloheximide, an inhibitor of protein synthesis, indicating that they are under the control of short-lived repressors.

scholarly journals A new genetic approach for studying hormonal regulation of urokinase-type plasminogen activator gene expression in LLC-PK1 cells.

1987 ◽  
Vol 7 (12) ◽  
pp. 4535-4541 ◽  
Author(s):  
P Hofstetter ◽  
Z Kikinis ◽  
M S Altus ◽  
D Pearson ◽  
Y Nagamine
Keyword(s):  
Protein Kinase ◽  
Plasminogen Activator ◽  
Hormonal Regulation ◽  
Regulatory Region ◽  
Regulatory Proteins ◽  
Protein Kinase Activity ◽  
Mrna Levels ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Upa Mrna

In LLC-PK1 cells, a cyclic AMP (cAMP)-elevating peptide hormone, calcitonin, induces urokinase-type plasminogen activator (uPA) gene transcription without concomitant protein synthesis. To understand the molecular mechanism of the uPA gene regulation by cAMP, we developed a system which allows us to obtain mutant cells with modified regulatory proteins. A uPA-gpt hybrid gene was constructed, in which the regulatory region of the uPA gene was linked to a bacterial xanthine-guanine phosphoribosyltransferase gene (gpt), and it was transfected into LLC-PK1 cells. A stably transformed cell line, which expressed gpt only in the presence of calcitonin, was obtained, and then these cells were treated with a chemical mutagen, ethyl methanesulfonate. Cells were screened for constitutive gpt expression and, as mutations in regulatory proteins should affect the two genes at the same time, cells were further screened for an increased basal uPA mRNA level. Several such clones were obtained and none of them had modified cAMP-dependent protein kinase activity, suggesting that mutations were in the post-protein kinase step in the pathway of hormone action. Five clones were fused with the parent LLC-PK1 cells, and all of the fusion cells showed reduced basal uPA mRNA levels, indicating that they were recessive mutants. One clone was analyzed further for sensitivity to calcitonin in the induction of uPA mRNA, and it showed a significantly different dose-response pattern compared with parent cells. These results suggest that the uPA gene is regulated, at least partly, by a negatively regulating factor and that the action of cAMP is linked to this factor.

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