Specificity of Calreticulin Transacetylase to acetoxy derivatives of benzofurans: Effect on the activation of platelet Nitric Oxide Synthase

Gupta, Anjali; Priya, Nivedita; Jalal, Sarah; Singh, Prabhjot; Chand, Karam; Raj, Hanumantharao G.; Parmar, Virinder S.; DePass, Anthony L.; Sharma, Sunil K.

doi:10.1016/j.biochi.2010.06.011

Cited by 10 publications

(4 citation statements)

References 23 publications

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“…Semi-synthetic acetyl derivatives of polyphenols such as 7, 8-diacetoxy-4-methylcoumarin (DAMC) and 7-acetoxy-4-methylcoumarin (7-AMC) have been shown to participate in protein acetylation of target proteins and alter their activity by virtue of novel acetoxy drug: calreticulin transacetylase (CRTase) acetylation system424344454647 in addition to the therapeutic benefits of the parent moiety. DAMC, a polyphenolic acetate (PA) has been shown to acetylate target enzymes such as NADPH-cyto-c reductase, nitric oxide synthase (NOS), glutathione S transferase, cyto-P-450 in a calreticulin dependent manner and modulate their physiological activity4849. DAMC up-regulates the expression and activity of anti-oxidant protein thioredoxin (TRX) in the peripheral blood mononuclear cells (PBMCs), accompanied by profound reduction in the levels of intracellular reactive oxygen species (ROS) levels thereby, minimising oxidative stress50.…”

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confidence: 99%

Mitigation of radiation-induced hematopoietic injury by the polyphenolic acetate 7, 8-diacetoxy-4-methylthiocoumarin in mice

Venkateswaran

Shrivastava

Agrawala

et al. 2016

Sci Rep

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Protection of the hematopoietic system from radiation damage, and/or mitigation of hematopoietic injury are the two major strategies for developing medical countermeasure agents (MCM) to combat radiation-induced lethality. In the present study, we investigated the potential of 7, 8-diacetoxy-4-methylthiocoumarin (DAMTC) to ameliorate radiation-induced hematopoietic damage and the associated mortality following total body irradiation (TBI) in C57BL/6 mice. Administration of DAMTC 24 hours post TBI alleviated TBI-induced myelo-suppression and pancytopenia, by augmenting lymphocytes and WBCs in the peripheral blood of mice, while bone marrow (BM) cellularity was restored through enhanced proliferation of the stem cells. It stimulated multi-lineage expansion and differentiation of myeloid progenitors in the BM and induced proliferation of splenic progenitors thereby, facilitating hematopoietic re-population. DAMTC reduced the radiation-induced apoptotic and mitotic death in the hematopoietic compartment. Recruitment of pro-inflammatory M1 macrophages in spleen contributed to the immune-protection linked to the mitigation of hematopoietic injury. Recovery of the hematopoietic compartment correlated well with mitigation of mortality at a lethal dose of 9 Gy, leading to 80% animal survival. Present study establishes the potential of DAMTC to mitigate radiation-induced injury to the hematopoietic system by stimulating the re-population of stem cells from multiple lineages.

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confidence: 99%

Mitigation of radiation-induced hematopoietic injury by the polyphenolic acetate 7, 8-diacetoxy-4-methylthiocoumarin in mice

Venkateswaran

Shrivastava

Agrawala

et al. 2016

Sci Rep

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“…Polyphenolic acetates (PAs) mediate protein acetylation by virtue of a novel acetoxy drug: calreticulin transacetylase system (CRTase) 21,23,24,27,28 and have been shown to cause hyper-acetylation of low molecular weight proteins such as histones 57 . Histone acetylation has several implications including chromatin remodelling, altered gene expression, role in DNA replication and activation of key signal transduction cascades relevant in a cell-context specific manner 58 .…”

Section: Resultsmentioning

confidence: 99%

“…Some of the target proteins (enzymes) observed to be acetylated by the polyphenolic acetate (PA) DAMC, in a calreticulin-dependent manner viz. nitric oxide synthase (NOS), glutathione S transferase, thioredoxin, and NADPH-cyto-c reductase 27,28 are well known modifiers of oxidative stress involved in the radiation response of cells 29,30 . More recently, DAMC has been shown to augment vascular endothelial growth factor (VEGF), thus, stimulating angiogenesis 29 that could facilitate recovery from radiation damage.…”

Section: Introductionmentioning

confidence: 99%

Mitigation of radiation-induced gastro-intestinal injury by the polyphenolic acetate 7, 8-diacetoxy-4-methylthiocoumarin in mice

Venkateswaran

Shrivastava

Agrawala

et al. 2019

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Radiation-induced intestinal injury (RIII) constitutes a crucial clinical element of acute radiation syndrome with life-threatening implications posing challenges in devising effective medical countermeasures. Herein, we report the potential of 7, 8-diacetoxy-4-methylthiocoumarin (DAMTC) to mitigate RIII following total-body irradiation (TBI) in C57BL/6 mice and underlying mechanisms. Administration of DAMTC 24 hours post TBI facilitated structural reconstitution and restoration of functional absorption linked to alleviation of radiation-induced apoptotic death of intestinal crypt progenitor/stem (ICPS) and villus stromal cells through induction of Bcl-2 family-mediated anti-apoptotic signalling. Reduction in TBI-induced DNA damage accumulation coupled with inhibition of cell cycle arrest through stimulation of anti-p53- and anti-p21-dependent synergistic signalling protected ICPS cells from radiation injury. Enhanced proliferation of crypt stem cells, induction of anti-oxidant defence, subjugation of TBI-induced lipid peroxidation and phenotypic polarization of intestinal macrophages to anti-inflammatory M2 class underlie amelioration of RIII. Stimulation of multiple mitigative signalling processes by DAMTC appeared to be associated with enhanced protein acetylation, an important regulator of cellular responses to radiation damage. Our findings establish the mitigative potential of DAMTC against RIII by hyper-acetylation-mediated epigenetic regulation, which triggers axes of anti-apoptotic and pro-survival pathways, enabling proliferation and maintenance of ICPS cells leading to epithelial regeneration.

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“…The conclusion is that in vivo platelets are regulated primarily by NO originating from the outside of platelets, mainly from the vascular endothelium [89]. As for rat platelets, there is only a very few reports of possible expression and activity of NOS in these cells [90,91]. The fact that there exist so many conflicting reports about the expression of NOS in platelets, also in rodent platelets, largely results from differences in experimental conditions and from nonspecific methods employed to detect NOS expression and activity.…”

Section: Nitric Oxide Synthase Activity In Blood Platelets-a Fact or mentioning

confidence: 99%

Only the Truth Would Enlighten Us — The Advantages and Disadvantages of Flow Cytometry as a Method of Choice in the Study of Mouse and Rat Platelets

Kassassir¹,

Siewiera²,

Przygodzki³

et al. 2016

Flow Cytometry - Select Topics

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Increasing number of transgenic and knockout strains of laboratory rodents has been developed to provide reliable models of human cardiovascular diseases. Due to apparent differences in platelet physiology, morphology, biochemistry, etc. between rodents and men, methods employed to study blood platelets in rodents should always consider these differences in a reasonably critical way. Flow cytometry is a convenient tool that enables to easily cope with the minute amounts of the available biological material and providing an extremely versatile information. This review focuses on the practical and methodological aspects of flow cytometry, pointing to the key elements of the commonly used protocols for determining of multiple parameters of blood platelet (patho)physiology in mice and rats. We summarized and critically reviewed the available procedures, as well as figured out how to overcome possible obstacles, shortcomings, drawbacks or artefacts that a researcher may encounter when monitoring various phenomena intimately associated with blood platelet biology. Flow cytometry assays have been also collated with some alternative techniques (intravital fluorescence microscopy, in vitro platelet adhesion under flow conditions). We hope that our paper may further facilitate other researchers to study mouse and rat platelets with the use of the most optimal and the least artefact-prone procedures.

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Specificity of Calreticulin Transacetylase to acetoxy derivatives of benzofurans: Effect on the activation of platelet Nitric Oxide Synthase

Cited by 10 publications

References 23 publications

Mitigation of radiation-induced hematopoietic injury by the polyphenolic acetate 7, 8-diacetoxy-4-methylthiocoumarin in mice

Mitigation of radiation-induced hematopoietic injury by the polyphenolic acetate 7, 8-diacetoxy-4-methylthiocoumarin in mice

Mitigation of radiation-induced gastro-intestinal injury by the polyphenolic acetate 7, 8-diacetoxy-4-methylthiocoumarin in mice

Only the Truth Would Enlighten Us — The Advantages and Disadvantages of Flow Cytometry as a Method of Choice in the Study of Mouse and Rat Platelets

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