223 research outputs found
"Virinder Moudgil - Career Highlights"
No full textNews article"Virinder K. Moudgil, Ph.D., a renowned researcher, author and mentor has brought recognition to Oakland for his research, and has been published hundreds of times for his articles on his breakthroughs in breast cancer research.
Comparative specificities of Calreticulin Transacetylase to O-acetyl, N-acetyl and S-acetyl derivative of 4-methylcoumarins and their inhibitory effect on AFB1-induced genotoxicity in vitro and in vivo.
No full textWe have earlier conclusively established the Calreticulin Transacetylase (CRTAase) catalyzed modifications of functional proteins such as cytochrome-P450-linked mixed function oxidases (Cyt-P450-linked MFOs), NADPH cytochrome c reductase, and glutathione S-transferase by acetoxy derivatives of polyphenols. In this study, we have investigated the comparative specificities of CRTAase to N-acetyl derivative, 7-acetamido-4-methylcoumarin (7-N-AMC), O-acetyl derivative, 7-acetoxy-4-methylcoumarin (7-AMC), S-acetyl derivative, 7-thioacetyl-4-methycoumarin (7-S-AMC) and their parent compounds in the modulation of catalytic activities of aforesaid proteins. Special attention concentrated on the comparative inhibitory effect of aforesaid acetyl moiety on Cyt-P450-linked MFOs such as 7-ethoxyresorufin O-deethylase (EROD), pentoxyresorufin O-dealkylase (PROD) and aflatoxin B1 (AFB1)-induced genotoxicity in vitro and in vivo. The results clearly indicated that N-acetyl and O-acetyl derivatives were better substrates for CRTAase while the S-acetyl was found to be a poorer substrate. Our study involving atomic charge, charge density and molecular electrostatic potential (MEP) calculations indicated the pivotal role of electronegativity and charge distribution values of O, N and S atoms of the acetyl group at C-7 position of the 4-methylcoumarins in CRTAase activity. These facts reinforce our hypothesis that the CRTAase catalyzed modifications of the catalytic activities of aforesaid proteins by acetyl derivative of 4-methylcoumarins is probably due to acetylation of these proteins. © 2012 Elsevier Ltd
The role of calreticulin transacetylase in the activation of human platelet nitrite reductase by polyphenolic acetates
No full textOur earlier investigations demonstrated the remarkable activation of cytochrome P-450 reductase and nitric oxide synthase by 7,8-diacetoxy-4-methylcoumarin, a model polyphenolic acetate by way of acetylation, catalyzed by the Calreticulin. Protein acetyltransferase action of Calreticulin was hence termed Calreticulin transacetylase (CRTAase). Nitric oxide synthase and nitrite reductase are now considered as parts of nitric oxide cycle. The activation of platelets nitric oxide synthase by 7,8-diacetoxy-4-methylcoumarin has already been demonstrated by us. Also, there are reports that certain proteins such as cytochrome P-450 reductase and cytochrome P-450 are endowed with the nitrite reductase activity in mammalian cells. Keeping these facts in view, we turned our attention to probe whether 7,8-diacetoxy-4-methylcoumarin could alter the levels of nitric oxide independent of the action of nitric oxide synthase in the human platelets model. The incubation of 7,8-diacetoxy-4-methylcoumarin and nitrite with platelets caused significant elevation of nitric oxide and cyclic guanosine monophosphate levels possibly due to the activation of nitrite reductase. Several polyphenolic acetates were similarly found to activate the nitrite reductase in tune with their affinities as substrate to CRTAase. N-omega-Nitro-L-arginine methyl ester, the inhibitor of nitric oxide synthase, failed to reverse such an effect of 7,8-diacetoxy-4-methylcoumarin. Clotrimazole which is known to be an inhibitor of nitrite reductase, effectively abolished the 7,8-diacetoxy-4-methylcoumarin mediated enhancement of nitric oxide levels in platelets as well as the nitric oxide mediated effects; such as cyclic guanosine monophosphate levels as well as adenosine diphospate induced platelets aggregation due to nitrite
Biological activity of natural and synthetic antoxidants in L-6 myoblasts in culture: redefining the role of Reactive Oxygen Species
No full textOxidative stress may be broadly defined as an imbalance between oxidant production and the antioxidant capacity of the cell to prevent oxidative injury; it is a condition believed to be involved in a large number of human diseases including atherosclerosis, cancer and neurodegenerative neuroinflammatory diseases, and also in aging. The situation of oxidative stress results in the production of O2 metabolites known as Reactive Oxygen Species (ROS) due to their enhanced reactivity compared to molecular oxygen; the most common are the superoxide anion (O2-.), hydrogen peroxide (H2O2), and the highly reactive hydroxyl radical (OH.). In order to protect themselves from ROS damage cells possess several antioxidant enzymes, such as superoxide dismutase (SOD), catalase and glutathione peroxidase, but also low molecular weight antioxidants like vitamin C and vitamin E.Much evidence suggests that ROS are not only injurious by-products of cellular metabolism but also essential participants in cell signaling and regulation and it is now clear that small amounts of ROS act as messenger molecules in cell signal transduction pathways. The plasma membrane of eukaryotic cells in particular contains a variety of different ROS-producing oxidases and reductases, of which the best characterized are the superoxide-producing NADPH oxidases. It has been known for many years that these membrane redox activities can be changed rapidly by various hormones and growth factors, but the molecular mechanisms involved and the physiological importance of this phenomenon have only recently begun to be unveiled. We here summarize the state of the art on membrane-based ROS signaling in the pathways of several hormones, mainly insulin and thyroid hormones. The apparent paradox of ROS being essential biomolecules in the regulation of cellular functions, but also toxic by-products of metabolism, may be important for the pharmacological application of natural and synthetic antioxidants. We report results on the capability of coumarins, flavonoids and other polyphenols to modulate the ROS production by some hormones and the signal transduction pathways involved
Calreticulin transacetylase catalyzed activation of rat tracheal smooth muscle cell nitric oxide synthase by acetoxycoumarins
No full textThe Transacetylase function of Calreticulin (CR) catalyzing the transfer of acetyl groups from acetoxycoumarins (AC) to certain proteins was identified for the first time in our laboratory. Protein acetyltransferase action of CR was termed Calreticulin Transacetylase (CRTAase). In the present work, CRTAase of rat tracheal smooth muscle cells (TSMC) was characterized with respect to the specificity for various AC and its role in the activation of nitric oxide synthase (NOS). 7,8-Diacetoxy-4-methylcoumarin (DAMC), a model AC, when incubated with TSMC along with L-arginine caused profound activation of NOS as compared to that with L-arginine alone. Further, the inclusion of N-omega-nitro-L-arginine methyl ester (L-NAME) along with DAMC resulted in the reduction of NO levels of TSMC to that of control, there by confirming the activation of TSMC NOS. Also, several AC were found to activate TSMC NOS in tune with their specificities to CRTAase. The results presented in this paper bear evidence for the activation of TSMC NOS by AC and their effectiveness to enhance NO of airway cells may be expected to find useful applications in respiratory diseases
4-Methylcoumarin Derivatives with Anti-inflammatory Effects in Activated Microglial Cells
No full textInflammation contributes to the pathogenesis of neurodegenerative diseases and anti-inflammatory compounds may have a role in prevention or treatment of these pathologies. 4-Methylcoumarins are effective antioxidants with anti-inflammatory properties. In this study, the inhibitory effects of two 4-methylcoumarin derivatives, 7,8-dihydroxy-3-ethoxycarbonylmethyl-4-methylcoumarin (DHEMC) and 7,8-diacetoxy-3-ethoxycarbonylmethyl-4-methylcoumarin (DAEMC) were examined on the inflammatory processes induced by lipopolysaccharide (LPS) in activated primary rat microglial cultures. LPS-induced production of nitric oxide (NO, measured by Griess method) and other pro-inflammatory mediators, thromboxane (TX) B2 and prostaglandin (PG) E2 (both determined by radioimmunoassay (RIA)), as well as tumor necrosis factor (TNF)-α (determined by enzyme-linked immunosorbent assay (ELISA)) were inhibited in the presence of 100 μM DHEMC and DAEMC. DAEMC was able to significantly inhibit NO, TXB2 and TNF-α production also at 50 μM. Both compounds at 100 μM significantly lowered cyclooxygenase-2 (COX-2) protein expression in LPS-stimulated microglial cells measured by Western blot, but only DAEMC showed an inhibitory effect on inducible nitric oxide synthase (iNOS) protein expression at 100 μM. In conclusion, our findings show that 4-methylcoumarin derivatives can modulate inflammatory pathways in microglial cells, probably by acting at the protein expression level
Comparison of Protein Acetyltransferase Action of CRTAase with the Prototypes of HAT
No full textOur 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
Protective effects of new antioxidant compositions of 4-methylcoumarins and related compounds with dl-α-tocopherol and l-ascorbic acid
No full textCoumarin derivatives possess a wide range of biological activities. By functionalization of the parent coumarin skeleton that has neither antioxidant nor biological activity, a series of new bio-antioxidants has been designed
Renal transplantation in a child with thrombosed inferior vena cava
No full textThe external iliac vein is commonly used in renal transplantation for vascular anastomosis of the allograft renal vein. However, there are rare instances when the transplant surgeon may encounter thrombosis of the ilio-caval vein during surgery, making renal transplantation a challenge. Often, these patients are considered unsuitable for renal transplantation. We report a case of thrombosis of the inferior vena cava in an asymptomatic pediatric patient in whom the splenic vein was used, at transplantation, for venous drainage. This case highlights that pre-operative Doppler screening should be performed in all potential renal transplant recipients
Legislators in India: A comparison of MLAs in five states.
No full textThis study, encompassing five of India's twenty-five states with 42.4% of its population, is the first comparative evaluation of India's state-level legislators (MLAs). So far research on MLAs has resulted in a series of studies in individual states largely focused on their changing socio-economic background and political socialization. The present enquiry extends this to examine their activities, effectiveness, role perceptions, and attitudes particularly in relation to national issues. The selected states were chosen to represent the diversity of India along regional, ethnic and linguistic lines and also to represent five different political parties in India which display different sub-cultures and ideologies: Uttar Pradesh - Hindi heartland, India's most populous state (population 139 million, 1991, ruling party BJP, 1991/2); Maharashtra - Western region, India's commercial capital (79 million, Cong.I); West Bengal - Eastern region, a longstanding and flourishing leftist government (68 million, CPI(M) led Left-front); Tamilnadu - Southern region, ruled by regional parties since 1967 (56 million, DMK); and Haryana - Northern region, a prosperous agricultural state (16 million: Janata Dal, 1990). The research is based upon face to face interviews of at least an hour's length with MLAs in these five states. The data reported are largely quantitative but rest upon qualitative and inter-active contents. The findings are three fold: first, provincial legislators, whether in Hindi heartland or elsewhere, have a commitment to the concept and unity of India; second, in the light of the secondary literature on legislative roles, MLAs in India are on balance closer to the "errand-boy" model than to the Westminster model of legislators holding, at least theoretically, the executive to account; third, there are significant variations in terms of socio-economic backgrounds and the perceptions of various state level and national issues between different states and different parties. MLAs, irrespective of their state or party and by virtue of their strategic position in the middle strata between the apex and base of society, are a vital and sensitive link in the process of political integration in India. These intermediate elites are largely "politically bilingual" with a capability to relate to both the elite above and the "masses" below. This makes them not only effective channels of communication but also an influential mediating linkage between the two. India's current population is over 850 million and this populous democracy is ultimately articulated by 545 MPs at national level. But the author argues that some 4000 provincial legislators, as an important component of India's intermediate elite, are crucial to the stability of India
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