Browsing by Author "Sharawan Yadav"

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Association of single nucleotide polymorphisms in CYP1B1 and COMT genes with breast cancer susceptibility in Indian women
(Hindawi Limited, 2009) Sharawan Yadav; Naveen Kumar Singhal; Virendra Singh; Neeraj Rastogi; Pramod Kumar Srivastava; Mahendra Pratap Singh
Cytochrome P450 1B1 (CYP1B1) and catechol-$O$- methyltransferase (COMT) enzymes play critical roles in estrogen metabolism. Alterations in the catalytic activity of CYP1B1 and COMT enzymes have been found associated with altered breast cancer risk in postmenopausal women in many populations. The substitution of leucine (Leu) to valine (Val) at codon 432 increases the catalytic activity of CYP1B1, however, substitution of Val to methionine (Met) at codon 158 decreases the catalytic activity of COMT. The present study was performed to evaluate the associations of CYP1B1 Leu 432Val and/or COMT Val158Met polymorphisms with total, premenopausal and postmenopausal breast cancer risks in Indian women. COMT and CYP1B1 polymorphisms in controls and breast cancer patients were analyzed employing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by gel electrophoresis. Although CYP1B1 and COMT genotypes did not exhibit statistically significant association with breast cancer risks when analyzed individually, COMT wild type (Val158Val) in combination with CYP1B1 heterozygous variant (Leu432Val) [OR: 0.21; 95% CI (0.05-0.82), p value; 0.021] and COMT heterozygous variant (Val 158Met) in combination with CYP1B1 wild type (Leu432Leu) [OR: 0.29; 95% CI (0.08-0.96), p value; 0.042] showed significant protective association with premenopausal breast cancer risk. The results demonstrate that CYP1B1 wild type in combination with COMT heterozygous or their inverse combination offer protection against breast cancer in premenopausal Indian women. © 2009 - IOS Press and the authors. All rights reserved.
Resveratrol potentiates cytochrome P450 2 d22-mediated neuroprotection in maneb- and paraquat-induced parkinsonism in the mouse
(2012) Garima Srivastava; Anubhuti Dixit; Sharawan Yadav; Devendra Kumar Patel; Om Prakash; Mahendra Pratap Singh
A strong association between polymorphisms of the cytochrome P450 (CYP/Cyp) 2D6 gene and risk to Parkinson's disease (PD) is well established. The present study investigated the neuroprotective potential of Cyp2d22, a mouse ortholog of human CYP2D6, in maneb- and paraquat-induced parkinsonism and the mechanisms involved therein along with the effects of resveratrol on various parameters associated with Cyp2d22-mediated neuroprotection. The animals were treated intraperitoneally with resveratrol (10 mg/kg, daily) and paraquat (10 mg/kg) alone or in combination with maneb (30 mg/kg), twice a week, for 9 weeks, along with their respective controls. The subsets of animals were also treated intraperitoneally with a Cyp2d22 inhibitor, ketoconazole (100 mg/kg, daily). Maneb and paraquat reduced Cyp2d22 and vesicular monoamine transporter type 2 (VMAT-2) expressions, the number of tyrosine hydroxylase-positive cells, and dopamine content and increased paraquat accumulation in the nigrostriatal tissues, oxidative stress, microglial activation, neuroinflammation, and apoptosis. Cyp2d22 inhibitor significantly exacerbated all these neurodegenerative indexes. Resveratrol cotreatment, partially but significantly, ameliorated the neurodegenerative changes by altering Cyp2d22 expression and paraquat accumulation. The results obtained in the study demonstrate that Cyp2d22 offers neuroprotection in maneb- and paraquat-induced dopaminergic neurodegeneration and resveratrol enhances its neuroprotective credentials by influencing Cyp2d22 expression and paraquat accumulation. © 2012 Elsevier Inc. All rights reserved.
Rodent models and contemporary molecular techniques: Notable feats yet incomplete explanations of Parkinson's disease pathogenesis
(Humana Press Inc., 2012) Sharawan Yadav; Anubhuti Dixit; Sonal Agrawal; Ashish Singh; Garima Srivastava; Anand Kumar Singh; Pramod Kumar Srivastava; Om Prakash; Mahendra Pratap Singh
Rodent models and molecular tools, mainly omics and RNA interference, have been rigorously used to decode the intangible etiology and pathogenesis of Parkinson's disease (PD). Although convention of contemporary molecular techniques and multiple rodent models paved imperative leads in deciphering the role of putative causative factors and sequential events leading to PD, complete and clear-cut mechanisms of pathogenesis are still hard to pin down. The current article reviews the implications and pros and cons of rodent models and molecular tools in understanding the molecular and cellular bases of PD pathogenesis based on the existing literature. Probable rationales for short of comprehensive leads and future possibilities in spite of the extensive applications of molecular tools and rodent models have also been discussed. © Springer Science+Business Media, LLC 2012.
Role of metabolites and significance of SH groups in the action of NADP+-linked isocitrate dehydrogenase of urdbean seeds (Phaseolus mungo L.)
(2011) Pramod Kumar Srivastava; Govind Kant Srivastava; Indra Mani; Sharawan Yadav; Asha Anand
NADP+-linked-isocitrate dehydrogenase (EC 1.1.1.42) is a key enzyme of the Tricarboxylic Acid Cycle (TCA) and has been purified from urdbean seeds and it is inhibited by ATP in a competitive manner having inhibitor constant (Ki 1.32 mM. Phosphoenol-pyruvate, an energy rich compound plays an important role in the regulation of this enzyme and this metabolite inhibited the enzyme activity of NADP+-linked-isocitrate dehydrogenase of urdbean with inhibitor constant (Ki 2.66 mM in a competitive manner. The mode of inhibition by various metabolites of Krebs cycle has been carried out and found that oxaloacetate and succinate inhibit ICDH urdbean enzyme in a competitive manner with respect to isocitrate and their Ki values are found to be 7.27 and 10.67 mM, respectively. Citrate inhibits the urdbean ICDH enzyme non competitively with Ki revalue equal to 3.33 mM. The SH groups play a important role in the activity of NADP+-linked-isocitrate dehydrogenase and blocking of this group with SH-reagents, leads to inactivation of urdbean ICDH enzyme. With excess iodoacetamide (1.00 mM) and N-ethylmaleimide (4.0 mM) inhibition of this enzyme follows first order kinetics, suggesting that there are four reactive SH groups per mole of enzyme which are equally reactive and there is no site- site interaction among the tetrameric isoicitrate dehydrogenase of urdbean. © 2011 Academic Journals Inc.
Role of secondary mediators in caffeine-mediated neuroprotection in maneb- and paraquat-induced Parkinson's disease phenotype in the mouse
(2012) Sharawan Yadav; Satya Prakash Gupta; Garima Srivastava; Pramod Kumar Srivastava; Mahendra Pratap Singh
Maneb and paraquat are known to induce Parkinson's disease (PD) phenotype, however, caffeine offers neuroprotection. Nitric oxide (NO) acts an important mediator in PD phenotype and tyrosine kinase (TK), nuclear factor kappa B (NF-kB), p38 mitogen activated protein kinase (p38 MAPK) are known to regulate its production. The present study aimed to elucidate the role of caffeine in the regulation of NO production and microglial activation and their subsequent contribution in dopaminergic neuroprotection. The animals were treated with caffeine and/or maneb and paraquat along with controls. In a few sets of experiments, the animals were also treated with aminoguanidine, an inhibitor of inducible NO synthase, pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kB, genistein, an inhibitor of TK or SB202190, an inhibitor of p38 MAPK. Tyrosine hydroxylase (TH)-immunoreactivity and anti-integrin αM (OX-42) staining were performed to assess the number of dopaminergic neurons and activation of microglia, respectively. NO was measured in terms of nitrite, however, the expressions of p38 MAPK, interleukin (IL)-1β, NF-kB and TK were checked by western blot analyses. Maneb and paraquat induced the number of degenerating dopaminergic neurons, microglial cells, nitrite content, expressions of IL-1β, p38 MAPK, NF-kB and TK and caffeine co-treatment reduced the level of such alterations. Reductions were more pronounced in the animals co-treated with aminoguanidine, PDTC, genistein or SB202190. The results obtained thus demonstrate that caffeine down-regulates NO production, neuroinflammation and microglial activation, which possibly contribute to neuroprotection. © Springer Science+Business Media, LLC 2011.