The role of calreticulin transacetylase in the activation of human platelet nitrite reductase by polyphenolic acetates.
Our 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.
Arora
Shvetambri
S
Department of Biochemistry, V. P. Chest Institute, University of Delhi, Delhi, India.
Tyagi
Yogesh Kumar
YK
Kumar
Ajit
A
Majumder
Syamantak
S
Saluja
Daman
D
Raj
Hanumantharao Guru
HG
Chatterjee
Suvro
S
Saso
Luciano
L
Prasad
Ashok Kumar
AK
Parmar
Virinder Singh
VS
D000123:Acetyltransferases / Q000097:blood*; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D037282:Calreticulin / Q000502:physiology*; D003374:Coumarins / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004566:Electrodes; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D009251:NADPH-Ferrihemoprotein Reductase / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009572:Nitrite Reductases / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D059808:Polyphenols
C114369:7,8-diacetoxy-4-methylcoumarin; D000975:Antioxidants; D037282:Calreticulin; D003374:Coumarins; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; D019001:Nitric Oxide Synthase; D009251:NADPH-Ferrihemoprotein Reductase; D009572:Nitrite Reductases; D000123:Acetyltransferases; C539012:calreticulin transacetylase, human; D006152:Cyclic GMP