title: Acetoxy drug: protein transacetylase catalyzed activation of human platelet nitric oxide synthase by polyphenolic peracetates.
abstract: An enhanced intracellular level of Nitric oxide (NO) is essential to ameliorate several pathological conditions of heart and vasculature necessitating the activation of NOS. We have projected in this report the acetylation of eNOS by polyphenolic peracetates (PA) catalyzed by the novel enzyme acetoxy drug: protein transacetylase (TAase) discovered in our laboratory as an unambiguous way of activating NOS which results in the manifestation of physiological action. The human platelet was chosen as the experimental system in order to validate the aforementioned proposition. PA caused profound irreversible activation of platelet NADPH cytochrome c reductase mediated by TAase. The convincing biochemical evidences are presented to show that PA could cause acetylation of the reductase domain of NOS leading to the activation of eNOS in tune with their specificities to platelet TAase. As a result, the enhanced level of NO due to activation of platelet eNOS by PA was found to inhibit the ADP-induced platelet aggregation. The present studies highlight for the first time the role of PA as the novel potent agent for enhancing the intracellular NO levels.
authors.affiliation: Department of Biochemistry, V.P. Chest Institute, University of Delhi, Delhi 110 007, India.
authors.forename: Pulkit
authors.initials: P
authors.lastname: Khurana
authors.forename: Ranju
authors.initials: R
authors.lastname: Kumari
authors.forename: Parag
authors.initials: P
authors.lastname: Vohra
authors.forename: Ajit
authors.initials: A
authors.lastname: Kumar
authors.lastname: Seema
authors.forename: Garima
authors.initials: G
authors.lastname: Gupta
authors.forename: Hanumantharao G
authors.initials: HG
authors.lastname: Raj
authors.forename: Bilikere S
authors.initials: BS
authors.lastname: Dwarakanath
authors.forename: Virinder S
authors.initials: VS
authors.lastname: Parmar
authors.forename: Daman
authors.initials: D
authors.lastname: Saluja
authors.forename: Mridula
authors.initials: M
authors.lastname: Bose
authors.forename: Anjana
authors.initials: A
authors.lastname: Vij
authors.forename: Nabo K
authors.initials: NK
authors.lastname: Chaudhary
authors.forename: Jawahar S
authors.initials: JS
authors.lastname: Adhikari
authors.forename: Yogesh K
authors.initials: YK
authors.lastname: Tyagi
authors.forename: Ekta
authors.initials: E
authors.lastname: Kohli
mesh_terms: D000085:Acetates / Q000737:chemistry / Q000494:pharmacology*; D000107:Acetylation; D000217:Acyltransferases / Q000378:metabolism*; D001792:Blood Platelets / Q000201:enzymology*; D015153:Blotting, Western; D002384:Catalysis; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D005419:Flavonoids / Q000737:chemistry*; D006801:Humans; D018613:Microscopy, Confocal; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010636:Phenols / Q000737:chemistry*; D059808:Polyphenols
chemical_list: D000085:Acetates; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D045304:Cytochromes c; D019001:Nitric Oxide Synthase; D000217:Acyltransferases