Transcriptional downregulation of stromelysin by tetracycline

Jonat, Carsten; Chung, Fung Lung; Baragi, Vijaykumar M.

doi:10.1002/(sici)1097-4644(19960301)60:3<341::aid-jcb6>3.0.co;2-w

Cited by 51 publications

(28 citation statements)

References 35 publications

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“…Inhibition of MMPs could also be related to inhibition of the transcription of MMP mRNAs. 30 In our study, doxycycline significantly reduced aortic MMP-2 upregulation and MMP-2 activity in the 2 types of arteries. This suggests that it could act on MMP-2 expression, activation, The values of M/L ratio and CSA at 28 days are also presented in Figure 1; *PϽ0.05 vs control; †PϽ0.05 vs L-NAME alone.…”

Section: Discussionsupporting

confidence: 60%

Different Involvement of Extracellular Matrix Components in Small and Large Arteries During Chronic NO Synthase Inhibition

et al. 2005

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Abstract-In essential hypertension, conduit arteries present hypertrophic remodeling (increased cross-sectional area), whereas small arteries undergo eutrophic remodeling. The involvement of matrix metalloproteinases (MMPs) and de-adhesion proteins, such as tenascin-C and thrombospondin, has been relatively well characterized in large artery remodeling, but their contribution is not known in small artery remodeling. Rats received N -nitro-L-arginine methyl ester (L-NAME; 50 mg/kg per day) in their drinking water on days 1, 3, 7, 14, and 28. Arterial MMP-2 activity was measured by ELISA, whereas levels of tenascin-C and thrombospondin were assessed by Western blotting. To determine the involvement of MMPs, additional L-NAME rats received the nonselective MMP inhibitor doxycycline (30 mg/kg per day) on days 7, 14, and 28. Already, at day 1, pressure was elevated. Media/lumen ratio of mesenteric arteries and the aorta increased gradually to reach significance at 28 days. However, the cross-sectional area increased only in the aorta, confirming the heterogeneous remodeling process. In small arteries, MMP-2 activity increased after 7 and 14 days of treatment and returned to baseline at 28 days, whereas the elevation was more progressive but sustained in the aorta. The level of thrombospondin paralleled that of MMP-2 in small arteries, whereas tenascin-C levels declined rapidly and stayed below control values. Doxycycline blunted large artery remodeling but had no influence on the development of eutrophic remodeling despite elevation of MMP-2 activity in the process. Thus, in contrast to large artery hypertrophic remodeling, in which the contributions of cellular de-adhesion and matrix breakdown is manifest, the contribution of MMPs in eutrophic remodeling appears less crucial. Key Words: nitric oxide synthase Ⅲ arteries V ascular remodeling is considered an adaptive response to elevation of arterial pressure to normalize the wall tension. In essential hypertension, large artery remodeling is characterized by an increase in media thickness-lumen diameter (M/L) ratio and cross-sectional area (CSA). This augmentation of media mass, or hypertrophic remodeling, is explained by changes in size or number of vascular smooth muscle cells (VSMCs) and matrix collagen deposition. 1 In resistance arteries (diameter Ͻ300 m), essential hypertension is associated with a reduced lumen and increased M/L ratio but without CSA increase, producing a type of remodeling designated as inward eutrophic remodeling. 2 To explain this different response between large and small arteries, it is suggested that small arteries are not submitted to an augmented wall stress because they are initially constricted. 3-5 Thus, we hypothesized that inward eutrophic remodeling, which appears as a fixed form of vasoconstriction, could proceed through specific modifications of VSMC-matrix interactions.As in essential hypertension, chronic inhibition of NO synthesis with the L-arginine analogue N -nitro-L-arginine methyl ester (L-NAME) produces hypertrophic re...

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Section: Discussionsupporting

confidence: 60%

Different Involvement of Extracellular Matrix Components in Small and Large Arteries During Chronic NO Synthase Inhibition

et al. 2005

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“…The observation that oral administration of doxycycline markedly reduces the level of total collagenase protein, and not only collagenase activity, in extracts of canine (34,35) and human (36) OA cartilage suggests that, in addition to inhibiting the activity of some MMPs, the drug affects the production and accumulation of MMPs. The effect may be exerted through reduction of enzyme stability, as indicated by studies with recombinant MMP-8 (15) and MMP-13 (37), through inhibition of transcription, as has been shown for MMP-3 in fibroblasts (38) and for MMP-13 in human OA chondrocytes (39), or through inhibition of translation, as has been shown for type X collagen in senescent chick chondrocytes (40).…”

Section: Discussionmentioning

confidence: 99%

Specificity of inhibition of matrix metalloproteinase activity by doxycycline: Relationship to structure of the enzyme

Smith¹,

Mickler²,

Hasty³

et al. 1999

Arthritis & Rheumatism

150

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Objective. To investigate the inhibition of matrix metalloproteinase 1 (MMP-1), MMP-8, and MMP-13 by doxycycline, and to determine whether the variable hemopexin-like domain of each MMP was responsible for the differences in susceptibility to doxycycline inhibition among these collagenases.Methods. Recombinant human MMP-1 (collagenase 1), MMP-8 (collagenase 2), and MMP-13 (collagenase 3), truncated forms of MMP-8 and MMP-13 lacking the hemopexin-like domain, and a mutant form of truncated MMP-13 were used in these studies. The activity of the full-length MMP in the presence of doxycycline was tested against type II collagen, a natural substrate for the enzymes. A small peptolide substrate was used to determine which structural features of the MMPs were related to sensitivity to doxycycline inhibition.Results The matrix metalloproteinases (MMPs) represent a family of structurally related enzyme proteins that share many structural and functional characteristics (1,2), but differ in substrate specificity and cellular origin. Each of the known MMPs has at least 3 structural domains: the propeptide domain, the catalytic domain, and the hemopexin-like domain. A proline-rich hinge region of variable length is present between the catalytic domain and the hemopexin-like domain. The catalytic domain and the propeptide domain are highly conserved, while the hemopexin-like domain shows significant variability. In the gelatinases, an additional gelatinbinding domain is inserted into the catalytic domain.Three collagenases share the unique ability to cleave the triple helical region of interstitial collagens. MMP-1 (collagenase 1) has been purified from fibroblasts of humans and other animals and is expressed by a variety of connective tissues and epithelia. MMP-8 (collagenase 2) was initially purified from neutrophils, but is also expressed in cartilage (3,4). MMP-13 (collagenase 3) was originally described as rat uterine collagenase (5), but has now been shown to also be produced by human breast carcinomas and to be a major product

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“…• Indirect effects on endogenous activators and inhibitors that regulate MMP's activity [8,[39][40][41].…”

mentioning

confidence: 99%

“…Hence, in present study docking analysis of violacein with MMP2 and MMP9 was performed to get the possibility of direct active site inhibition to treat cerebral ischemia. A study by Kiyama et al suggested that MMP9 consists of S1'cavity pocket with a floor board and MMP2 have S1'channel like cavity [41]. The S1' pocket of MMP9 consists of Asp185 to Leu188 and Pro421 to Tyr423 residues which are effective for inhibition and substrate binding [43].…”

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confidence: 99%

An In-silico Approach to Explore the Possible Multifunctional Neuroprotective Efficacy of Violacein against Ischemic Stroke

Verma¹,

Ak²

2017

J In Silico In Vitro Pharmacol

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Introduction: Cerebral ischemia arise due to insufficient/ interrupted blood supply to brain and is accompanied by pathologies like degradation of extracellular matrix resulting in blood brain barrier disruption, intra cranial haemorrhage, activation of astroglial cells and hence death of neurons. In addition, oxidative stress and inflammation is common to all neurodegenerative diseases enhancing the harmful consequences of diseases. Matrix Metalloproteinases (MMP) are normally involved in extracellular matrix remodelling and are regulated while injury and inflammation in tissue. Over expression of MMP2 and MMP9 results in progression of ischemic conditions by extracellular matrix degradation thus compromising the structural integrity of Blood Brain Barrier (BBB) proving them a potent targets for the disease. Violacein (source: Chromobacterium violaceum), purple pigment from microbial origin is a bisindole have high anti-inflammatory, anti-oxidant, anti-bacterial, anticancer and anti-parasitic properties. Present study is to study the effective potential of violacein against cerebral ischemia.

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Transcriptional downregulation of stromelysin by tetracycline

Cited by 51 publications

References 35 publications

Different Involvement of Extracellular Matrix Components in Small and Large Arteries During Chronic NO Synthase Inhibition

Different Involvement of Extracellular Matrix Components in Small and Large Arteries During Chronic NO Synthase Inhibition

Specificity of inhibition of matrix metalloproteinase activity by doxycycline: Relationship to structure of the enzyme

An In-silico Approach to Explore the Possible Multifunctional Neuroprotective Efficacy of Violacein against Ischemic Stroke

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