Dr Madhu Dikshit
 


Scientist G & Scientist-in-Charge
Division of Pharmacology
Central Drug Research Institute
Lucknow 226 001

 
Educational qualifications M.Sc., Ph.D.
E-mail madhu_dikshit@cdri.res.in
Date of Birth 21.11.1957
 
CURRENT AREAS OF INTEREST
•
 Role of NO in the physiological as well as pathological conditions
(thrombosis, ischemia, hypertension, and neurodegeneration)
•
 Molecular mechanisms involved in the regulation of NADPH-oxidase and
NOS activity in the neutrophils
•
 Peripheral markers in the CNS disorder
  Functional flow cytometry
Basic Studies in CVS
Studies on platelets and neutrophils
• Collagen induced platelet activation: Molecular Mechanisms involved and their modulation by CDRI anti-platelet molecules
• Effect of NO on neutrophil free radical generation and neutrophil extracellular traps (NETs) release
Molecular, biochemical characterization and distribution of nitric oxide synthase in neutrophils and their precursor cells



NO mediated modulation of HL60 cell cycle: Role of CDK2 nitrosylation
Neutrophils (PMNs), indispensable for host defense, act primarily by the generation of reactive oxygen species (ROS) and nitrogen species (RNS) to kill invaded pathogens. Studies from this lab have demonstrated significant alterations in the release of NO specifically from PMNs in experimental models of sepsis, thrombosis, hypoxia-reoxygenation, and in Parkinson’s disease patients. Immunocytochemical, molecular and biochemical studies have unraveled unique features of NOS – localization, expression of splice variants and regulation of enzymatic NO synthesis. Recent studies on PMNs from various species, including human, have demonstrated role of ascorbic acid in regulation of the enzymatic synthesis of NO by stabilizing tetrahydrobiopterin, a cofactor of NOS. Modulation of NO availability to PMNs influences NADPH-oxidase activity, myeloperoxidase release and activity to modulate free radical generation from PMNs, which by led to the formation of neutrophil extracellular traps.
Papers published
1. Patel S, Vemula J, Konikkat S, Barthwal MK, Dikshit M: Ion channel modulators mediated alterations in NO induced free radical generation and neutrophil membrane potential. Free Rad Res, 43: 514-521, 2009.
2. Chatterjee M, Saluja R, Kumar V, Jyoti A, Kumar Jain G, Barthwal MK, Dikshit M. Ascorbate sustains neutrophil NOS expression, catalysis, and oxidative burst. Free Radic Biol Med. 2008;45:1084-93.
3. Gupta R, Chakrabarti P, Dikshit M, Dash D: Late signaling in the activated platelets upregulates tyrosine phosphatase SHP1 and impairs platelet adhesive functions: Regulation by calcium and Src kinase. Biochim Biophys Acta - Mol Cell Res 1773: 131-140, 2007.
4. Saini R, Patel S, Saluja R, Sahasrabuddhe AA, Singh MP, Habib S, Bajpai VK, Dikshit M: Nitric oxide synthase localization in the rat neutrophils: immunocytochemical, molecular and biochemical studies. J Leukocyte Biol 79:519-28, 2006.
5. Sharma P, Raghavan SAV, Dikshit M: Ascorbate-mediated enhancement of reactive oxygen species generation from polymorphonuclear leukocytes: modulatory effect of nitric oxide. J Leuko Biol 75, 1070-1078, 2004.
RESEARCH EXPERIENCE
 
•
 Biochemical Pharmacology
 
SELECTED PUBLICATIONS
 
•
 Chatterjee Madhumita, Saluja Rohit, Kumar Vipul, Jyoti Anupam, Jain Girish Kumar, Barthwal Manoj Kumar and Dikshit Madhu - Ascorbate sustains neutrophil NOS expression, catalysis, and oxidative burst (2008) - Free Radical Biology & Medicine 45, 1084-1093
•
 Kumar S, Gupta K Barthwal MK and Dikshit M - Nitric oxide synthesis in neutrophil precursor cells and effect of nitric oxide modulators on their maturation (2008) - FASEB J 22, 749-5
•
 Patel S, Kumar S, Saluja R, Barthwal MK, Mitra K, Verma A, Bajpai VK and Dikshit M - Neutrophil extracellular trap formation by nitric oxide donors: Involvement of nitric oxide synthase and myeloperoxidase derived free radicals (2008) - FASEB J. 22, 1072-9
•
 Surin WR, Barthwal MK and Dikshit M - Platelet collagen receptors, signalling and antagonism: Emerging approaches for the prevention of intra-vascular thrombosis (2008) - Thrombosis Res 122, 786-803
•
 Chatterjee M, Saluja R, Kanneganti S, Chinta S and Dikshit Madhu - Biochemical and molecular evaluation of neutrophil NOS in spontaneously hypertensive rats. (2007) - Cellular and Molecular Biology 15, 84-93
•
 Das A, Dikshit Madhu and Nath C. - Alteration in acetylcholinesterase glycosylation of rat brain in memory disorder. (2007) - FASEB Journal 21, A788-A788
•
 Gupta R, Chakrabarti P, Dikshit M and Dash D. - Late signaling in the activated platelets up regulates tyrosine phosphatase SHP1 and impairs platelet adhesive functions: Regulation by calcium and Src kinase. (2007) - Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1773, 131-140
•
 Patel S, Kumar S, Barthwal MK and Dikshit M - New insight into the NO-mediated signaling to modulate neutrophil free radical generation. (2007) - FASEB Journal 21, A623-A623
•
 Sankaranarayanan A, Narender T, Kumar S and Dikshit M - Allium sativum constituents: Effect on free radical generation from rat neutrophils. (2007) - Cellular and Molecular Biology 53, 63-67
•
 Santhanam Vijay R, Anantha Viswanathan, Shivkumar and Dikshit, Madhu - Activation of protein kinase B/Akt and endothelial nitric oxide synthase mediates agmatine-induced endothelium-dependent relaxation . (2007) - European Journal of Pharmacology 572, 189-196
•
 Sharma Preeti, Singh Sangeeta, Siddiqui Tanveer I, Singh Vishnu S, Kundu Bijoy, Prathipati Philip, Saxena Anil K, Dikshit Dinesh K, Rastogi Leena, Dixit Chetna, Gupta MB, Patnaik GK and Dikshit Madhu. - a-Amino acid derivatives as proton pump inhibitors and potent anti-ulcer agents. (2007) - European Journal of Medicinal Chemistry 42, 386-393
•
 Singh Sarika and Dikshit Madhu - Apoptotic neuronal death in Parkinson's disease: Involvement of nitric oxide. (2007) - Brain Research Reviews 54, 233-250
•
 Kavya, Ramkumar , Saluja, Rohit, Singh, Sarika and Dikshit , Madhu - Nitric oxide synthase regulation and diversity: Implications in Parkinson’s disease (2006) - Nitric Oxide, 15, 280-294
•
 Saini, R; Patel, S; Saluja, R; Sahasrabuddhe, A, Singh, A; M P; Habib, S; Bajpai, V K; Dikshit, M - Nitric oxide synthase localization in the rat neutrophils: immunocytochemical, molecular, and biochemical studies (2006) - Journal Of Leukocyte Biology, 79, 519-528.
•
 Sharma P, Raghavan SAV and Dikshit M: Role of ascorbate in the regulation of nitric oxide generation by polymorphonuclear leukocytes. Biochem Biophys Res Commun (in press), 2003.
•
 Sharma P, Barthwal MK and Dikshit M: NO Synthesis and its regulation in the arachidonic acid stimulated rat polymorphonuclear leukocytes. Nitric Oxide Biol. Chem., 7, 119-126, 2002.
•
 Singh MP, Sinha S, Raghavan SAV and Dikshit M: Inhibition of platelet aggregation by rat globin. Thrombosis Research 107, 201-207, 2002.
•
 Raghavan SAV and Dikshit M: Augmented relaxation to L-citrulline in lipopolysaccharide treated rat aorta: possible role of L-citrulline in endotoxaemia. Eur J Pharmacol. 431, 61-69, 2001.
•
 Sethi S, Singh MP and Dikshit M: Nitric oxide mediated augmentation of polymorphonuclear free radical generation following hypoxia-reoxygenation. Blood 93, 333-340, 1999.
•
 Barthwal MK, Srivastava N, Shukla R, Nag D, Seth PK, Srimal RC and Dikshit M: Polymorphonuclear leukocyte nitrite content and antioxidant enzymes in Parkinson's disease patients. Acta Neurol Scand. 100, 300-304, 1999.
•
 Seth P, Kumari R, Dikshit M and Srimal RC: Modulation of rat polymorphonuclear leukocyte response by nitric oxide and arginine. Blood 84, 2741-2748, 1994.
•
 Dikshit M, Kumari R and Srimal RC: Pulmonary thromboembolism induced alterations in the nitric oxide release from the rat neutrophils. J Pharmacol Exp Therap 265, 1369-1373, 1993.
 
PATENTS FILED / ACCEPTED
 
•
 A process for the preparation of novel 1-arylalkyl-5-oxo-proline carboxamides useful as thrombin inhibitors. Dinesh Kumar Dikshit, Madhu Dikshit, Prashant Sharma, Stuti Srivastava, (Product patent [NF/492/01] and Process patent [NF/486/01] Filed for Indian Patent on 29.11.2001)
•
 WGI/75K Novel herbal composition for the treatment of Gastric Ulcer. JM Rao, U Sampath Kumar, BS Sastry, JS Yadav, KV Raghavan, G Palit, M Dikshit, D Rai, PM Varier, TS Muraleedharan, K Muraleedharan [filed for the international patent in USA and European countries].