کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1926452 | 1536464 | 2009 | 7 صفحه PDF | دانلود رایگان |

Miltefosine has been shown to be a very active compound against Trypanosoma cruzi. Here, we evaluated the effects of miltefosine on the activity of the Na+-ATPase and protein kinase C (PKC) present in the plasma membrane of T. cruzi. Furosemide (2 mM), a specific inhibitor of Na+-ATPase, abolished the growth of T. cruzi showing a crucial role of this enzyme to parasite growth. Miltefosine inhibited the Na+-ATPase activity with IC50 = 18 ± 5 μg mL−1. This effect was shown to be reversible, dependent on the pH and Ca2+. The inhibition was not observed when the membranes were solubilized with 0.1% deoxycholate, suggesting that the interaction between the enzyme and membrane phospholipids might be important for the drug effect. Miltefosine also inhibited the parasite PKC activity, but through a Na+-ATPase-independent way. Altogether the results indicate that miltefosine inhibits T. cruzi growth through, at least in part, the inhibition of both Na+-ATPase and PKC activities.
Journal: Archives of Biochemistry and Biophysics - Volume 481, Issue 1, 1 January 2009, Pages 65–71