Investigation of the Mechanism of Action of Microperoxidase-11, (MP11), a Potential Anti-cataract Agent, with Hydrogen Peroxide and Ascorbate

Spector, Abraham; Zhou, Wei; Ma, Wu; Chignell, Colin F.; Reszka, Krzysztof J.

doi:10.1006/exer.2000.0867

Cited by 25 publications

(16 citation statements)

References 33 publications

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“…Acidic pH has been shown to up-regulate VEGF and basic fibroblast growth factor expression in human endothelial cells (29) and various tumor cells (15,30), as well as interleukin-8 expression in human ovarian carcinoma cells (31) and in human pancreatic cancer cells (32). On the other hand, some studies also show that acidic pH decreases the expression of VEGF and extracellular matrix proteins gene expression in mouse osteoblasts (33,34). It has been suggested that the lower pH and decreased VEGF production serve to regulate osteogenesis negatively in areas that first require resorption by resident osteoclasts (33).…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, some studies also show that acidic pH decreases the expression of VEGF and extracellular matrix proteins gene expression in mouse osteoblasts (33,34). It has been suggested that the lower pH and decreased VEGF production serve to regulate osteogenesis negatively in areas that first require resorption by resident osteoclasts (33). These observations suggest that variable responses of different cells to the same stimuli are relevant to different biological functions.…”

Section: Discussionmentioning

confidence: 99%

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Acidic Extracellular pH Induces Vascular Endothelial Growth Factor (VEGF) in Human Glioblastoma Cells via ERK1/2 MAPK Signaling Pathway

Fukumura

Jain

2002

Journal of Biological Chemistry

257

197

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Overexpression of vascular endothelial growth factor (VEGF) is associated with disease progression in human glioblastomas. We recently showed that VEGF promoter activity is inversely correlated with tumor extracellular pH (pH o ) in vivo in the human glioma (U87 MG) xenografts. Here we show that substitution of the neutral culture medium (pH 7.3) with acidic pH medium (pH 6.6) up-regulates VEGF mRNA and protein production in human glioblastoma cells as reflected by Northern blot analysis and enzyme-linked immunosorbent assay. Functional analysis of the VEGF promoter reveals that the sequence between ؊961 bp and ؊683 bp upstream of the transcription start site is responsible for the transcriptional activation of the VEGF gene by acidic pH. This region contains the binding site for AP-1. Consequently, AP-1 luciferase reporter gene was activated by acidic pH. Gel-shift analysis confirmed that AP-1 DNA binding activity is induced under acidic pH. While investigating the upstream signaling pathways, we found that ERK1/2 MAPK is activated and translocates to the nucleus to activate Elk-1, and inhibition of the activation of ERK by specific inhibitors of MEK1 blocks the up-regulation of VEGF by low pH. Dominant negative forms of Ras and Raf abolished the activation of VEGF promoter by acidic pH. These results show that acidic pH activates Ras and the ERK1/2 MAPK pathway to enhance VEGF transcription via AP-1, leading to increased VEGF production.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Acidic Extracellular pH Induces Vascular Endothelial Growth Factor (VEGF) in Human Glioblastoma Cells via ERK1/2 MAPK Signaling Pathway

Fukumura

Jain

2002

Journal of Biological Chemistry

257

197

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“…With an increase in the HVA concentration to 64 mm, reduction in catalytic activity was again observed, which confirmed the hypothesis that both excessive substrate and specific inhibitors will compete with hydrogen peroxide for the sixth proximal ligand-binding site through coordination interaction, thus hindering the formation of compounds I and II, which are essential for hemin-catalyzed reactions. [33,34] As a result, inhibition of catalytic activity occurred. In contrast, when we performed the inhibiting experiments with FA for N-MIP, no obvious decrease was observed either in the reaction rate or in the fluorescent product formation.…”

Section: Introductionmentioning

confidence: 97%

“…[33,41,42] In this work, we investigated the recovery of the catalytic activity of HVA-imprinted MIP over several reaction runs, and found that a number of polymer samples could be recovered from reaction mixtures, exhaustively re-extracted, and reused for similar reactions. Notably, under the reaction conditions and over the time course employed in these studies, negligible breakdown of MIP materials was observed in the first several runs when sufficient reductant substrate was present in the reaction system.…”

Section: Introductionmentioning

confidence: 99%

“…[33] We ascribe this to a scheme in which a putative ™compound I∫ of the hemin with H 2 O 2 is reduced by reductant substrate www.chemeurj.org such as HVA and Vc into ™compound II∫ and then back to their original redox state (ferric) in two one-electron steps; in the absence of reductants, the ™compound I∫ reacts further with the hydrogen peroxide causing hemin degradation and evolution of O 2 . [33,34] …”

Section: Introductionmentioning

confidence: 99%

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Synthesis of an Enzyme‐like Imprinted Polymer with the Substrate as the Template, and Its Catalytic Properties under Aqueous Conditions

Cheng

Zhang

2004

Chemistry A European J

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Transition state analogues (TSAs) have long been regarded as ideal templates for the preparation of catalytically active synthetic imprinted polymers. In the current work, however, a new type of molecularly imprinted polymer (MIP) was synthesized with the substrate (homovanillic acid, HVA) as the template and hemin introduced as the catalytic center, with the use of plural functional monomers to prepare the active sites. The MIP successfully mimicked natural peroxidase, suggesting that it may not be imperative to employ a TSA as the template when preparing enzyme-like imprinted polymers and that the imprinted polymer matrix provided an advantageous microenvironment around the catalytic center (hemin), essentially similar to that supplied by apo-proteins in natural enzymes. Significantly, by taking advantage of the special structure of hemin and multiple-site interactions provided by several functional monomers, the intrinsic difficulties for MIPs in recognizing template molecules in polar solutions were overcome. The newly developed polymer showed considerable recognizing ability toward HVA, catalytic activity, substrate specificity and also stability, which are the merits lacked by the natural peroxidase. Meanwhile, the ease of recovery and reuse the MIP implies the potential for industrial application.

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Functionalization of Oxidases with Peroxidase Activity Creates Oxiperoxidases: A New Breed of Hybrid Enzyme Capable of Cascade Chemistry

et al. 2011

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The covalent flavoprotein alditol oxidase (AldO) from Streptomyces coelicolor A3(2) was endowed with an extra catalytic functionality by fusing it to a microperoxidase. Purification of the construct resulted in the isolation of a synthetic bifunctional enzyme that was both fully covalently flavinylated and heminylated: an oxiperoxidase. Characterization revealed that both oxidase and peroxidase functionalities were active, with the construct functioning as a single-component xylitol biosensor. In an attempt to reduce the size of the oxidase-peroxidase fusion, we replaced portions of the native AldO sequence with the bacterial cytochrome c CXXCH heme-binding motif. By mutating only three residues of the AldO protein we were able to create a functional oxidase-peroxidase hybrid.

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Investigation of the Mechanism of Action of Microperoxidase-11, (MP11), a Potential Anti-cataract Agent, with Hydrogen Peroxide and Ascorbate

Cited by 25 publications

References 33 publications

Acidic Extracellular pH Induces Vascular Endothelial Growth Factor (VEGF) in Human Glioblastoma Cells via ERK1/2 MAPK Signaling Pathway

Acidic Extracellular pH Induces Vascular Endothelial Growth Factor (VEGF) in Human Glioblastoma Cells via ERK1/2 MAPK Signaling Pathway

Synthesis of an Enzyme‐like Imprinted Polymer with the Substrate as the Template, and Its Catalytic Properties under Aqueous Conditions

Functionalization of Oxidases with Peroxidase Activity Creates Oxiperoxidases: A New Breed of Hybrid Enzyme Capable of Cascade Chemistry

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