Artemisinin can inhibit the calmodulin-mediated activation of phosphodiesterase in comparison with Cyclosporin A.
Artemisinin and Cyclosporin A were examined for their ability to inhibit the calmodulin-mediated activation of phosphodiesterase, which is based on the hydrolysis of cAMP to AMP by phosphodiesterase in the presence or absence of inhibitors, followed by quantitative analysis using spectrophotometer method. Anti-calmodulin activity of these agents was investigated by spectrofluorometry. Our results indicates that Artemisinin and Cyclosporin A induced some conformational changes on calmodulin and increased the fluorescence emission, but Artemisinin increased fluorescence emission of calmodulin in higher amounts compared with the Cyclosporin A. Kinetic analysis of the Artemisinin-calmodulin and Cyclosporine A-calmodulin interaction showed that these agents competitively inhibited the activation of phosphodiesterase without affecting Vmax. Artemisinin increased Km value in higher amounts compared with the Cyclosporin A. Ki values of Artemisinin and Cyclosporin A were determined as 10 microM and 35 microM, respectively. The DeltaG (H2O), the best parameter for the estimation of macromolecule stability, was determined for calmodulin in the absence and presence of Artemisinin and Cyclosporin A. However, the degree of decrease in DeltaG (H2O) value was as follows: Artemisinin>Cyclosporin A, which means Artemisinin induced more instability in the calmodulin structure.In conclusion, our findings showed a good correlation between the ability of both Artemisinin and Cyclosporin A to block the activation of phosphodiesterase and their ability to bind to the activator and that Artemisinin is a more potent inhibitor of phosphodiesterase compared with Cyclosporin A.
Noori
S
S
Department of Biochemistry, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran. noori@modares.ac.ir
Hassan
Z M
ZM
Rezaei
B
B
Rustaiyan
A
A
Habibi
Z
Z
Fallahian
F
F
D000890:Anti-Infective Agents / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects*
D000890:Anti-Infective Agents; D037621:Artemisinins; D002147:Calmodulin; D010726:Phosphodiesterase Inhibitors; D016572:Cyclosporine; C031327:artemisinin; D010727:Phosphoric Diester Hydrolases