Calreticulin transacetylase catalyzed modification of the TNF-α mediated pathway in the human peripheral blood mononuclear cells by polyphenolic acetates

Singh, Usha; Kumar, Ajit; Sinha, Rajesh; Manral, Sushma; Arora, Shvetambri; Ram, Sant; Mishra, Rakesh K.; Gupta, Prachi; Bansal, Surendra K.; Prasad, Ashok K.; Biswal, Shyam; Parmar, Virinder S.; Raj, Hanumantharao G.

doi:10.1016/j.cbi.2010.02.025

Cited by 20 publications

(14 citation statements)

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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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“…Thus, inhibition of the release of inflammatory cytokines is an important strategy to protect heart against myocardial damage in T2DM patients. As an important inflammatory cytokine, TNF-α is produced mainly by the activation of monocytes/macrophages, and participates in certain autoimmune diseases (29)(30)(31)(32)(33). Thus, it could stimulate the NO synthase (i-NOS) to synthesize and release a large number of NO.…”

Section: Discussionmentioning

confidence: 99%

Effects of propofol on myocardial ischemia-reperfusion injury in rats with type-2 diabetes mellitus

Wang

et al. 2016

Biomedical Reports

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Abstract. The current study aimed to examine the effects of propofol on myocardial ischemia-reperfusion injury (MIRI) in rats with type-2 diabetes mellitus (T2DM) and to assess the role of inflammatory mediators. Fifty healthy male adult Sprague-Dawley rats were randomly divided into the sham, ischemia-reperfusion (IR), IR plus low, middle and high-dose (6, 12 and 24 mg/kg/h, intravenous) propofol groups. The rats of all the groups were fed a high-sugar and high-fat diet for 8 weeks and streptozotocin (30 mg/kg, intraperitoneally) was used to establish the T2DM model. Apart from the sham group rats, MIRI was induced by ligating the left anterior descending coronary artery for 30 min, followed by reperfusion for 2 h. Heart rate (HR), left ventricular systolic pressure (LVSP), and the rate of left ventricular pressure increase in early systole (± dp/dt max ) were recorded. Levels of cardiac troponin T (cTnT), nitric oxide (NO), endothelin-1 (ET-1), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were also measured. Myocardial lesions were observed under light microscopy and scanning electron microscopy. Compared with levels prior to arterial occlusion, HR, LVSP, and ± dp/dt max were significantly reduced (P<0.05) following occlusion for 30 min and reper fusion for 2 h. The administration of propofol ameliorated the cardiac function of rats as reflected by the increase in HR, LVSP and ± dp/dt max . In addition, the administration of propofol increased the serum NO concentration, and reduced ET-1 and cTnT levels, as well as levels of inflammatory mediators including IL-1β, IL-6 and TNF-α. Thus, propofol exerts protective effects against MIRI in T2DM rats by increasing NO and reducing ET-1 and the inflammatory mediators.

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“…Recently, we have reported that DAMC could modulate tumor necrosis factor-alpha induced activation of iNOS [17] leading to elevated cellular NO levels. Also, DAMC inhibits TNF- α mediated release of IL-6 probably by inhibiting TNF- α stimulated activation of some specific kinases (MAP kinases), thus contributing to the anti-inflammatory effect of PA [18]. Further, protein kinase C (PKC) was inhibited probably by CRTAase mediated acetylation by DAMC.…”

Section: Physiological Significance Of Crtaase Mediated Acetylatiomentioning

confidence: 99%

“…Nitric oxide (NO) generated from L-arginine by NOS in the endothelium and in other cells plays a central role in several aspects of vascular biology [16]. Our investigations on the NO-related biological actions such as vasorelaxation, inhibition of ADP-induced platelet aggregation in vitro and in vivo [13, 17], activation of iNOS, and inhibition of TNF- α induced IL-6 in human peripheral blood mono nuclear cells (PBMC) [18] lead us to formulate the cardinal role of PA in influencing the NOS-related protein functions by way of acetylation mediated by TAase. The identity of TAase with an endoplasmic reticulum luminal protein, calreticulin (CR), was evidenced by proteomic analysis such as N-terminal sequencing, immunoreactivity with anti-calreticulin antibody, and mass spectrometry [19–21], and this novel function of CR was termed calreticulin transacetylase (CRTAase).…”

Section: Introductionmentioning

confidence: 99%

Comparison of Protein Acetyltransferase Action of CRTAase with the Prototypes of HAT

Ponnan

Kumar

Singh

et al. 2014

The Scientific World Journal

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Our laboratory is credited for the discovery of enzymatic acetylation of protein, a phenomenon unknown till we identified an enzyme termed acetoxy drug: protein transacetylase (TAase), catalyzing the transfer of acetyl group from polyphenolic acetates to receptor proteins (RP). Later, TAase was identified as calreticulin (CR), an endoplasmic reticulum luminal protein. CR was termed calreticulin transacetylase (CRTAase). Our persistent study revealed that CR like other families of histone acetyltransferases (HATs) such as p300, Rtt109, PCAF, and ESA1, undergoes autoacetylation. The autoacetylated CR was characterized as a stable intermediate in CRTAase catalyzed protein acetylation, and similar was the case with ESA1. The autoacetylation of CR like that of HATs was found to enhance protein-protein interaction. CR like HAT-1, CBP, and p300 mediated the acylation of RP utilizing acetyl CoA and propionyl CoA as the substrates. The similarities between CRTAase and HATs in mediating protein acylation are highlighted in this review.

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Calreticulin transacetylase catalyzed modification of the TNF-α mediated pathway in the human peripheral blood mononuclear cells by polyphenolic acetates

Cited by 20 publications

References 31 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

Effects of propofol on myocardial ischemia-reperfusion injury in rats with type-2 diabetes mellitus

Comparison of Protein Acetyltransferase Action of CRTAase with the Prototypes of HAT

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