Acetoxy drug: protein transacetylase catalyzed activation of human platelet nitric oxide synthase by polyphenolic peracetates.
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.
Khurana
Pulkit
P
Department of Biochemistry, V.P. Chest Institute, University of Delhi, Delhi 110 007, India.
Kumari
Ranju
R
Vohra
Parag
P
Kumar
Ajit
A
Seema
Gupta
Garima
G
Raj
Hanumantharao G
HG
Dwarakanath
Bilikere S
BS
Parmar
Virinder S
VS
Saluja
Daman
D
Bose
Mridula
M
Vij
Anjana
A
Chaudhary
Nabo K
NK
Adhikari
Jawahar S
JS
Tyagi
Yogesh K
YK
Kohli
Ekta
E
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
D000085:Acetates; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D045304:Cytochromes c; D019001:Nitric Oxide Synthase; D000217:Acyltransferases