scholarly journals Sequential Amyloid-β Degradation by the Matrix Metalloproteases MMP-2 and MMP-9

2015 ◽  
Vol 290 (24) ◽  
pp. 15078-15091 ◽  
Author(s):  
Mar Hernandez-Guillamon ◽  
Stephanie Mawhirt ◽  
Steven Blais ◽  
Joan Montaner ◽  
Thomas A. Neubert ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Matrix Metalloproteases ◽  
The Matrix

scholarly journals Levels of Gene Expression of Immunological Biomarkers in Peri-Implant and Periodontal Tissues

2020 ◽  
Vol 17 (23) ◽  
pp. 9100
Author(s):  
Luciene Cristina Figueiredo ◽  
Bruno Bueno-Silva ◽  
Cristiana Fernandes Plutarco Nogueira ◽  
Leonardo Carneiro Valadares ◽  
Katia Marina Morilla Garcia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Matrix Metalloproteases ◽  
Gingival Tissue ◽  
Mrna Levels ◽  
Necrosis Factor Alpha ◽  
Periodontal Tissues ◽  
Tnf Α ◽  
The Matrix ◽  
Study Population ◽  
Factor Alpha

This study compared the gene expression of the immunoinflammatory markers interleukin (IL)-6, IL-1ß, and tumor necrosis factor alpha (TNF-α), the matrix metalloproteinases (MMP)-1, -2, -8, and -9, and the tissue inhibitors of matrix metalloproteases (TIMP)-1 and -2 in the gingival tissue of individuals with periodontal and peri-implant disease. The study population included individuals with four periodontal statuses: periodontal health (PH group, n = 20); periodontitis (P group, n = 20); peri-implant health (PIH group, n = 20), and peri-implantitis (PI group, n = 20). Gingival biopsies were collected from one tooth per patient according to the inclusion criteria of each group. The mRNA levels of IL-6, IL-1ß, TNF-α, MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 were evaluated by qPCR. The levels of IL-1ß were significantly higher in the PI group when compared to the other groups (p < 0.05), while the levels of IL-6 were significantly higher in the groups with periodontal and peri-implant disease when compared with the healthy groups (p < 0.05); however, the levels of IL-6 did not differ between the PI and P groups (p > 0.05). For all other studied biomarkers, no significant differences were observed between groups (p > 0.05). IL-6 and IL-1ß presented higher levels of mRNA in diseased periodontal and peri-implant tissues. However, the expression of metalloproteinases and their inhibitors did not differ between the different periodontal statuses.

scholarly journals The novel mitochondrial matrix protease Ste23 is required for efficient presequence degradation and processing

2017 ◽  
Vol 28 (8) ◽  
pp. 997-1002 ◽  
Author(s):  
Asli Aras Taskin ◽  
Cansu Kücükköse ◽  
Nils Burger ◽  
Dirk Mossmann ◽  
Chris Meisinger ◽  
...  
Keyword(s):  
Human Insulin ◽  
Feedback Inhibition ◽  
Amyloid Β ◽  
The Novel ◽  
Mitochondrial Matrix ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Precursor Proteins ◽  
The Matrix ◽  
Processing Protease

Approximately 70% of mitochondrial precursor proteins are imported from the cytosol via N-terminal presequences, which are cleaved upon exposure to the mitochondrial processing protease MPP in the matrix. Cleaved presequence peptides then need to be efficiently degraded, and impairment of this clearance step, for example, by amyloid β peptides, causes feedback inhibition of MPP, leading ultimately to accumulation of immature precursor proteins within mitochondria. Degradation of mitochondrial peptides is performed by Cym1 in yeast and its homologue, PreP, in humans. Here we identify the novel mitochondrial matrix protease Ste23 in yeast, a homologue of human insulin-degrading enzyme, which is required for efficient peptide degradation. Ste23 and Cym1 tightly cooperate to ensure the correct functioning of the essential presequence processing machinery.

scholarly journals Ovulation is Inhibited by an Environmentally Relevant Phthalate Mixture in Mouse Antral Follicles in Vitro

2020 ◽  
Author(s):  
Katie L Land ◽  
Madison E Lane ◽  
Ava C Fugate ◽  
Patrick R Hannon
Keyword(s):  
Endocrine Disrupting Chemicals ◽  
Consumer Products ◽  
Matrix Metalloproteases ◽  
Dependent Manner ◽  
Ecm Remodeling ◽  
Antral Follicles ◽  
The Matrix ◽  
Housing Materials ◽  
Ovulatory Period

Abstract Phthalates are solvents and plasticizers found in consumer products including cosmetics, food/beverage containers, housing materials, etc. Phthalates are known endocrine-disrupting chemicals that can directly target the ovary, potentially causing defects in ovulation and fertility. Women are exposed to multiple different phthalates daily, therefore this study investigated the effects of an environmentally relevant phthalate mixture (PHTmix) on ovulation. Ovulation is initiated by the luteinizing hormone (LH) surge, which induces prostaglandin (PG) production, progesterone (P4)/progesterone receptor (PGR) signaling, and extra-cellular matrix (ECM) remodeling. We hypothesized that the PHTmix would directly inhibit ovulation by altering the levels of PGs, P4/PGR, and enzymes involved in ECM remodeling. Antral follicles from CD-1 mice were treated with vehicle control alone (dimethylsulfoxide, DMSO), hCG alone (LH analog), and hCG+PHTmix (1-500μg/ml), and samples were collected across the ovulatory period. The PHTmix decreased ovulation rates at all doses tested in a dose dependent manner when compared to hCG. PG levels were decreased by the PHTmix when compared to hCG, which was potentially mediated by altered levels of PG synthesis (Ptgs2) and transport (Slco2a1) genes. The PHTmix altered P4 and Pgr levels when compared to hCG, leading to decreases in downstream PGR-mediated genes (Edn2, Il6, Adamts1). ECM remodeling was potentially dysregulated by altered levels of ovulatory mediators belonging to the matrix metalloproteases and plasminogen activator families. These data suggest that phthalate exposure inhibits ovulation by altering PG levels, P4/PGR action, and ECM remodeling.

scholarly journals Matrix Metalloproteases as Influencers of the Cells’ Social Media

2019 ◽  
Vol 20 (16) ◽  
pp. 3847 ◽  
Author(s):  
Daniel Young ◽  
Nabangshu Das ◽  
Anthonia Anowai ◽  
Antoine Dufour
Keyword(s):  
Inflammatory Diseases ◽  
Matrix Metalloproteases ◽  
Phase Iii ◽  
Biological Functions ◽  
Mmp Inhibitors ◽  
Ecm Remodeling ◽  
Surface Receptors ◽  
Phase Iii Clinical Trials ◽  
The Matrix ◽  
The Impact

Matrix metalloproteinases (MMPs) have been studied in the context of cancer due to their ability to increase cell invasion, and were initially thought to facilitate metastasis solely through the degradation of the extracellular matrix (ECM). MMPs have also been investigated in the context of their ECM remodeling activity in several acute and chronic inflammatory diseases. However, after several MMP inhibitors failed in phase III clinical trials, a global reassessment of their biological functions was undertaken, which has revealed multiple unanticipated functions including the processing of chemokines, cytokines, and cell surface receptors. Despite what their name suggests, the matrix aspect of MMPs could contribute to a lesser part of their physiological functions in inflammatory diseases, as originally anticipated. Here, we present examples of MMP substrates implicated in cell signaling, independent of their ECM functions, and discuss the impact for the use of MMP inhibitors.

scholarly journals Matrix Metalloproteinases in Diabetic Kidney Disease

2020 ◽  
Vol 9 (2) ◽  
pp. 472 ◽  
Author(s):  
Garcia-Fernandez ◽  
Jacobs-Cachá ◽  
Mora-Gutiérrez ◽  
Vergara ◽  
Orbe ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Interstitial Fibrosis ◽  
Experimental Models ◽  
Basement Membranes ◽  
Matrix Metalloproteases ◽  
Mesangial Expansion ◽  
Tubular Atrophy ◽  
Diabetic Kidney ◽  
The Matrix

Around the world diabetic kidney disease (DKD) is the main cause of chronic kidney disease (CKD), which is characterized by mesangial expansion, glomerulosclerosis, tubular atrophy, and interstitial fibrosis. The hallmark of the pathogenesis of DKD is an increased extracellular matrix (ECM) accumulation causing thickening of the glomerular and tubular basement membranes, mesangial expansion, sclerosis, and tubulointerstitial fibrosis. The matrix metalloproteases (MMPs) family are composed of zinc-dependent enzymes involved in the degradation and hydrolysis of ECM components. Several MMPs are expressed in the kidney; nephron compartments, vasculature and connective tissue. Given their important role in DKD, several studies have been performed in patients with DKD proposing that the measurement of their activity in serum or in urine may become in the future markers of early DKD. Studies from diabetic nephropathy experimental models suggest that a balance between MMPs levels and their inhibitors is needed to maintain renal homeostasis. This review focuses in the importance of the MMPs within the kidney and their modifications at the circulation, kidney and urine in patients with DKD. We also cover the most important studies performed in experimental models of diabetes in terms of MMPs levels, renal expression and its down-regulation effect.

scholarly journals Expression of the Matrix Metalloproteases 2, 14, 24, and 25 and Tissue Inhibitor 3 as Potential Molecular Markers in Advanced Human Gastric Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Sol de la Peña ◽  
Clara Luz Sampieri ◽  
Mariana Ochoa-Lara ◽  
Kenneth León-Córdoba ◽  
José María Remes-Troche
Keyword(s):  
Gastric Cancer ◽  
Molecular Markers ◽  
Matrix Metalloproteases ◽  
Human Gastric Cancer ◽  
Mrna Levels ◽  
Qrt Pcr ◽  
The Matrix ◽  
Chronic Superficial Gastritis ◽  
Strength Of Association ◽  
Very High

Background. During progression of gastric cancer (GC), degradation of the extracellular matrix is mediated by the matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs): changes in the expression of these have been related to unfavorable prognosis in GC.Objective. To analyze the expression of certain MMPs and TIMPs in chronic superficial gastritis (SG) and GC.Methods. The expression of MMPs and TIMPs was determined using qRT-PCR; the expression was classified, using threshold cycle (CT) values, as very high (CT≤25), high (CT=26–30), moderate (CT=31–35), low (CT=36–39), or not detected (CT=40). Strength of association was estimated between the proteins, which were detected by Western blot, and the risk of developing GC.Results. We found a high expression ofMMP1,MMP2,MMP14,TIMP1,andTIMP3; moderate one ofMMP9andMMP25,and low one ofMMP13andMMP24in both tissues. In absolute mRNA levels, significant differences were found in expression ofMMP2,MMP24,andMMP25, which are overexpressed in GC compared with SG. The presence of the proteins MMP-14 and TIMP-3 was associated with the risk of developing GC.Conclusions. We consider thatMMP2,MMP24,andMMP25and the proteins MMP-14 and TIMP-3 could be candidates for prognostic molecular markers in GC.

scholarly journals The Matrix Metalloproteases and Endothelin-1 in Infection-Associated Preterm Birth

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Nicole S. Olgun ◽  
Sandra E. Reznik
Keyword(s):  
Preterm Birth ◽  
Preterm Labor ◽  
Intrauterine Infection ◽  
The United States ◽  
Matrix Metalloproteases ◽  
Common Cause ◽  
Live Births ◽  
Endothelin 1 ◽  
The Matrix ◽  
Lines Of Evidence

Preterm birth (PTB) is clinically defined as any delivery which occurs before the completion of 37 weeks of gestation, and is currently the most important problem in obstetrics. In the United States, PTB accounts for 12-13% of all live births, and, with the exception of fetuses suffering from anomalies, is the primary cause of perinatal mortality. While the risk factors for PTB are numerous, the single most common cause is intrauterine infection. As there is currently no FDA-approved therapy for infection-associated PTB, understanding the pathogenesis of preterm labor (PTL) and delivery should be given high priority. The matrix metalloproteinases (MMPs) are a family of enzymes that have been implicated in normal parturition as well as infection-triggered rupture of membranes and preterm birth. Several lines of evidence also suggest a role for endothelin-1 (ET-1) in infection-associated preterm delivery. This paper focuses on the evidence that the MMPs and ET-1 act in the same molecular pathway in preterm birth.

Crystalloid Inclusions in Hepatocyte Mitochondria and Their Similarity to Cytoplasmic Crystalloids

1974 ◽  
Vol 32 ◽  
pp. 198-199
Author(s):  
Odell T. Minick ◽  
Hidejiro Yokoo
Keyword(s):  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Special Interest ◽  
Structural Variations ◽  
Mitochondrial Alterations ◽  
The Matrix ◽  
Crystalloid Inclusions ◽  
Liver Biopsies

Mitochondrial alterations were studied in 25 liver biopsies from patients with alcoholic liver disease. Of special interest were the morphologic resemblance of certain fine structural variations in mitochondria and crystalloid inclusions. Four types of alterations within mitochondria were found that seemed to relate to cytoplasmic crystalloids.Type 1 alteration consisted of localized groups of cristae, usually oriented in the long direction of the organelle (Fig. 1A). In this plane they appeared serrated at the periphery with blind endings in the matrix. Other sections revealed a system of equally-spaced diagonal lines lengthwise in the mitochondrion with cristae protruding from both ends (Fig. 1B). Profiles of this inclusion were not unlike tangential cuts of a crystalloid structure frequently seen in enlarged mitochondria described below.

Coherency loss in γ' precipitates in nickel-base superalloy

1983 ◽  
Vol 41 ◽  
pp. 244-245
Author(s):  
R. A. Ricks ◽  
Angus J. Porter
Keyword(s):  
Lattice Mismatch ◽  
Lattice Parameter ◽  
Nickel Base Superalloy ◽  
Large Size ◽  
The Matrix ◽  
Nimonic 80A ◽  
Interfacial Dislocations ◽  
Nickel Base ◽  
Coherency Loss ◽  
Nimonic 115

During a recent investigation concerning the growth of γ' precipitates in nickel-base superalloys it was observed that the sign of the lattice mismatch between the coherent particles and the matrix (γ) was important in determining the ease with which matrix dislocations could be incorporated into the interface to relieve coherency strains. Thus alloys with a negative misfit (ie. the γ' lattice parameter was smaller than the matrix) could lose coherency easily and γ/γ' interfaces would exhibit regularly spaced networks of dislocations, as shown in figure 1 for the case of Nimonic 115 (misfit = -0.15%). In contrast, γ' particles in alloys with a positive misfit could grow to a large size and not show any such dislocation arrangements in the interface, thus indicating that coherency had not been lost. Figure 2 depicts a large γ' precipitate in Nimonic 80A (misfit = +0.32%) showing few interfacial dislocations.

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