scholarly journals Dilating the degradome: matrix metalloproteinase 2 (MMP-2) cuts to the heart of the matter

2004 ◽  
Vol 383 (3) ◽  
Author(s):  
Christopher M. OVERALL
Keyword(s):  
Myocardial Fibrosis ◽  
Matrix Metalloproteinase 2 ◽  
Signalling Molecules ◽  
Biochemical Journal ◽  
Vasodilator Activity ◽  
Potent Vasodilator ◽  
Extracellular Matrix Remodelling ◽  
Treat Blood Pressure ◽  
Small Product

With recent work revealing that MMPs (matrix metalloproteinases) cleave an increasingly large degradome of bioactive and signalling molecules, the dogma that MMPs are extracellular-matrix-remodelling proteases is under challenge. In this issue of the Biochemical Journal, Martínez et al. have reported that AM (adrenomedullin), a potent vasodilator predominantly expressed by blood vessel endothelial and smooth muscle cells, and microvasculature-rich tissues, is another new bioactive substrate for MMPs in vivo. Cleavage by MMP-2, but not MMP-9, generates a series of peptides; two of which retain receptor agonist and vasodilator activity, three are inactive and, excitingly, AM(11–22), a small product containing a canonical disulphide loop, is a vasoconstrictor. In view of the robust vasodilatory and other cardiac protective activities of AM in inhibiting myocardial fibrosis this represents a potent new systemic role for MMP-2 in the cardiovasculature. Hence, the paper by Martínez et al. directly implicates MMP activity in the development of hypertension and paradoxically in stimulating myocardial fibrosis, therefore pointing to exciting new possibilities for utilizing MMP-2-specific inhibitors as a new mode to treat blood pressure and heart disease.

Resveratrol Reduces Matrix Metalloproteinase-2 Activity Induced by Oxygen-Glucose Deprivation and Reoxygenation in Human Cerebral Microvascular Endothelial Cells

2012 ◽  
Vol 82 (4) ◽  
pp. 267-274 ◽  
Author(s):  
Zahide Cavdar ◽  
Mehtap Y. Egrilmez ◽  
Zekiye S. Altun ◽  
Nur Arslan ◽  
Nilgun Yener ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Neurovascular Unit ◽  
Glucose Deprivation ◽  
Matrix Metalloproteinase 2 ◽  
Microvascular Endothelial Cells ◽  
Oxygen Glucose Deprivation ◽  
Microvascular Endothelial

The main pathophysiology in cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Among the human matrix metalloproteinases (MMPs), MMP-2 and -9, known as gelatinases, are the key enzymes for degrading type IV collagen, which is the major component of the basal membrane that surrounds the cerebral blood vessel. In the present study, we investigated the effects of resveratrol on cytotoxicity, reactive oxygen species (ROS), and gelatinases (MMP-2 and -9) in human cerebral microvascular endothelial cells exposed to 6 hours of oxygen-glucose deprivation and a subsequent 24 hours of reoxygenation with glucose (OGD/R), to mimic ischemia/reperfusion in vivo. Lactate dehydrogenase increased significantly, in comparison to that in the normoxia group. ROS was markedly increased in the OGD/R group, compared to normoxia. Correspondingly, ROS was significantly reduced with 50 μM of resveratrol. The proMMP-2 activity in the OGD/R group showed a statistically significant increase from the control cells. Resveratrol preconditioning decreased significantly the proMMP-2 in the cells exposed to OGD/R in comparison to that in the OGD/R group. Our results indicate that resveratrol regulates MMP-2 activity induced by OGD/R via its antioxidant effect, implying a possible mechanism related to the neuroprotective effect of resveratrol.

L-Tetrahydropalmatine Inhibits the Progression of Glioblastoma Tumor by Suppressing the Extracellular-Signal-Regulated Kinase/Nuclear Factor-Kappa B Signaling Pathway

2020 ◽  
Vol 19 (2) ◽  
pp. 164-171
Author(s):  
Feng Xue ◽  
Tingting Chen
Keyword(s):  
Glioblastoma Multiforme ◽  
Nuclear Factor Kappa B ◽  
Matrix Metalloproteinase 2 ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Extracellular Signal ◽  
Apoptosis Protein ◽  
Endothelial Growth Factor

Glioblastoma multiforme is the most common malignancy of central nervous system. Herein we have evaluated the effect of L-tetrahydropalmatine, an isoquinoline alkaloid, on the tumor growth both in vivo and in vitro using C6 glioblastoma multiforme cells and BALB/c mice injected subcutaneously with C6/luc2 cells. The results of these studies show that L-tetrahydropalmatine exhibited cytotoxic effect on C6 glioblastoma multiforme cells, suppressed nuclear factor-kappa B activity, suppressed the levels of tumor-linked proteins such as matrix metalloproteinase-2/9, Cyclin-D1, vascular endothelial growth factor, and X-linked inhibitor of apoptosis protein via ERK/nuclear factor-kappa B cascade. Further, L-tetrahydropalmatine inhibited the cell migration and invasion properties of C6 cells, and also suppressed the tumor weight and volume in mice. Immunohistochemical staining of tumor tissues suggested that L-tetrahydropalmatine inhibited the extracellular-signal-regulated kinase/nuclear factor-kappa B cascade and suppressed the levels of Cyclin-D1; matrix metalloproteinase-2/9; X-linked inhibitor of apoptosis protein; and vascular endothelial growth factor, and also the progression and growth of glioblastoma multiforme in mice. In summary, L-tetrahydropalmatine inhibits the ERK/nuclear factor-kappa B cascade, decreases the tumor volume, and inhibits the proteins responsible for tumor growth both in vivo and in vitro.

scholarly journals Myocardial fibrosis reversion via rhACE2-electrospun fibrous patch for ventricular remodeling prevention

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zeping Qiu ◽  
Jingwen Zhao ◽  
Fanyi Huang ◽  
Luhan Bao ◽  
Yanjia Chen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Myocardial Fibrosis ◽  
Ventricular Remodeling ◽  
Cardiac Fibroblasts ◽  
Cost Effective ◽  
Intramyocardial Injection ◽  
Undesirable Consequence ◽  
Adverse Remodeling

AbstractMyocardial fibrosis and ventricular remodeling were the key pathology factors causing undesirable consequence after myocardial infarction. However, an efficient therapeutic method remains unclear, partly due to difficulty in continuously preventing neurohormonal overactivation and potential disadvantages of cell therapy for clinical practice. In this study, a rhACE2-electrospun fibrous patch with sustained releasing of rhACE2 to shape an induction transformation niche in situ was introduced, through micro-sol electrospinning technologies. A durable releasing pattern of rhACE2 encapsulated in hyaluronic acid (HA)—poly(L-lactic acid) (PLLA) core-shell structure was observed. By multiple in vitro studies, the rhACE2 patch demonstrated effectiveness in reducing cardiomyocytes apoptosis under hypoxia stress and inhibiting cardiac fibroblasts proliferation, which gave evidence for its in vivo efficacy. For striking mice myocardial infarction experiments, a successful prevention of adverse ventricular remodeling has been demonstrated, reflecting by improved ejection fraction, normal ventricle structure and less fibrosis. The rhACE2 patch niche showed clear superiority in long term function and structure preservation after ischemia compared with intramyocardial injection. Thus, the micro-sol electrospun rhACE2 fibrous patch niche was proved to be efficient, cost-effective and easy-to-use in preventing ventricular adverse remodeling.

scholarly journals In vivo quantitative ultrasonic evaluation of myocardial fibrosis in humans.

Circulation ◽  
1990 ◽  
Vol 81 (1) ◽  
pp. 58-64 ◽  
Author(s):  
E Picano ◽  
G Pelosi ◽  
M Marzilli ◽  
F Lattanzi ◽  
A Benassi ◽  
...  
Keyword(s):  
Myocardial Fibrosis ◽  
Ultrasonic Evaluation

Dimerization of TOC receptor GTPases and its implementation for the control of protein import into chloroplasts

2011 ◽  
Vol 436 (2) ◽  
pp. e1-e2 ◽  
Author(s):  
Henrik Aronsson ◽  
Paul Jarvis
Keyword(s):  
Protein Import ◽  
Control Point ◽  
Nucleotide Exchange ◽  
Biochemical Journal ◽  
Exact Function ◽  
Translocation Mechanism ◽  
Loaded State ◽  
Outer Envelope Membrane ◽  
And Function

Pre-protein import into chloroplasts is facilitated by multiprotein translocon complexes in the envelope membranes. Major components of the TOC (translocon at the outer envelope membrane of chloroplasts) complex are the receptor proteins Toc33 and Toc159. These two receptors are related GTPases, and they are predicted to engage in homodimerization and/or heterodimerization. Although such dimerization has been studied extensively, its exact function in vivo remains elusive. In this issue of the Biochemical Journal, Oreb et al. present evidence that homodimerization of Toc33 prevents nucleotide exchange, thereby locking the receptor in the GDP-loaded state and preventing further activity. Pre-protein arrival is proposed to release this lock, through disruption of the dimer and subsequent nucleotide exchange. The Toc33-bound pre-protein is then able to progress to downstream steps in the translocation mechanism, with GTP hydrolysis defining another important control point as well as preparing the receptor for the next pre-protein client. These new results are discussed in the context of previous findings pertaining to TOC receptor dimerization and function.

scholarly journals Lidocaine Alleviates Sepsis-Induced Acute Lung Injury in Mice by Suppressing Tissue Factor and Matrix Metalloproteinase-2/9

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Binbin Zheng ◽  
Hongbo Yang ◽  
Jianan Zhang ◽  
Xueli Wang ◽  
Hao Sun ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Matrix Metalloproteinase ◽  
Gelatin Zymography ◽  
Neutrophil Infiltration ◽  
Negative Regulator ◽  
Matrix Metalloproteinase 2 ◽  
Cytokine Signaling

Acute lung injury (ALI) is one of the fatal symptoms of sepsis. However, there were no effective clinical treatments. TF accumulation-induced fibrin deposit formations and coagulation abnormalities in pulmonary vessels contribute to the lethality of ALI. Suppressor of cytokine signaling 3 (SOCS3) acts as an endogenous negative regulator of the TLR4/TF pathway. We hypothesized that inducing SOCS3 expression using lidocaine to suppress the TLR4/TF pathway may alleviate ALI. Hematoxylin and eosin (H&E), B-mode ultrasound, and flow cytometry were used to measure the pathological damage of mice. Gelatin zymography was used to measure matrix metalloproteinase-2/9 (MMP-2/9) activities. Western blot was used to assay the expression of protein levels. Here, we show that lidocaine could increase the survival rate of ALI mice and ameliorate the lung injury of ALI mice including reducing the edema, neutrophil infiltration, and pulmonary thrombosis formation and increasing blood flow velocity. Moreover, in vitro and in vivo, lidocaine could increase the expression of p-AMPK and SOCS3 and subsequently decrease the expression of p-ASK1, p-p38, TF, and the activity of MMP-2/9. Taken together, our study demonstrated that lidocaine could inhibit the TLR4/ASK1/TF pathway to alleviate ALI via activating AMPK-SOCS3 axis.

Nerve Growth Factor Enhances Calcitonin Gene-Related Peptide Expression in the Spontaneously Hypertensive Rat

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 701-701
Author(s):  
M Huawei Zhao ◽  
M Scott C Supowit ◽  
M Donald J DiPette
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Day Treatment ◽  
Fold Increase ◽  
Spontaneously Hypertensive ◽  
Treatment Groups ◽  
Continuous Map ◽  
Potent Vasodilator ◽  
Peptide Expression ◽  
Cgrp Receptor Antagonist

P45 We previously reported that there is a marked decrease in neuronal (dorsal root ganglia [DRG] sensory neurons) CGRP expression in the SHR compared to WKY controls. This reduction in such a potent vasodilator could contribute to the elevated BP. We hypothesize that administration of NGF, a potent in vivo stimulator of CGRP expression, to SHR would decrease the BP. NGF (10 nM/kg/day, i.p.) was given to 12 week SHR (n=8-11/group) once a day for 1, 3, and 7 days. Control SHR received vehicle only. All rats were instrumented for CGRP receptor antagonist (CGRP 8-37 ) administration (i.v.) and continuous MAP (arterial) recording and were studied in a concious and unrestrained state. Both the 1 and 3 day NGF treatments lowered the MAP (147±5 and 147±3 mmHg; respectively, p<0.05) compared to the controls (166±3 mmHg). However, by day 7 the MAP had returned to control levels (169±5 mmHg). To determine whether CGRP was involved in the BP lowering response to NGF, saline or CGRP 8-37 (bolus dose of 200 μg) were administered i.v. to all rats. Saline was without effect in any of the groups studied. In contrast, CGRP 8-37 administration produced a significant increase in MAP in both the 1 (13±1 mmHg) and 3 (10±1 mmHg) day NGF treatment groups. Surprisingly, in the 7 day treatment group, CGRP 8-37 also increased the MAP (13±2 mmHg) despite the baseline BP being back up to control levels. Quantification of CGRP mRNA and peptide levels in DRG revealed a significant (p<0.05) 1.5-fold increase on days 1 and 3 and a 1.75-fold increase on day 7. These data demonstrate that NGF treatment of SHR can significantly increase neuronal CGRP expression. At days 1 and 3, NGF produces a marked depressor response that is primarily due to CGRP as evidenced by the pressor effect of CGRP 8-37 . In the day 7 group, CGRP also plays a counterregulatory role even though the MAP has returned to control levels. This may result from an NGF-mediated upregulation of a pressor system that counteracts the hypotensive actions of CGRP. These results, therefore, suggest that the decreased production of CGRP in the SHR could contribute to the elevated BP observed in this hypertensive model.

scholarly journals Molecular mechanisms of olfactory detection in insects: beyond receptors

Open Biology ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 200252
Author(s):  
Hayden R. Schmidt ◽  
Richard Benton
Keyword(s):  
Molecular Mechanisms ◽  
Olfactory Receptors ◽  
Environmental Chemicals ◽  
Ecological Niches ◽  
Cellular Mechanisms ◽  
Signalling Molecules ◽  
Olfactory Systems ◽  
Lymph Fluid ◽  
And Function

Insects thrive in diverse ecological niches in large part because of their highly sophisticated olfactory systems. Over the last two decades, a major focus in the study of insect olfaction has been on the role of olfactory receptors in mediating neuronal responses to environmental chemicals. In vivo , these receptors operate in specialized structures, called sensilla, which comprise neurons and non-neuronal support cells, extracellular lymph fluid and a precisely shaped cuticle. While sensilla are inherent to odour sensing in insects, we are only just beginning to understand their construction and function. Here, we review recent work that illuminates how odour-evoked neuronal activity is impacted by sensillar morphology, lymph fluid biochemistry, accessory signalling molecules in neurons and the physiological crosstalk between sensillar cells. These advances reveal multi-layered molecular and cellular mechanisms that determine the selectivity, sensitivity and dynamic modulation of odour-evoked responses in insects.

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