Catestatin, an endogenous chromogranin A-derived peptide, inhibits in vitro growth of Plasmodium falciparum.
Catestatin, an endogenous peptide derived from bovine chromogranin A, and its active domain cateslytin display powerful antimicrobial activities. We have tested the activities of catestatin and other related peptides on the growth of Plasmodium falciparum in vitro. Catestatin inhibits growth of the chloroquine-sensitive strain of P. falciparum 3D7, exhibiting 88% inhibition at 20 microM. A similar partial inhibition of parasite growth was observed for the chloroquine-resistant strain, 7G8 (64%,) and the multidrug-resistant strain, W2 (62%). In the presence of parasite-specific lactate dehydrogenase, a specific protein-protein interaction between catestatin and plasmepsin II precursor was demonstrated. In addition, catestatin partially inhibited the parasite-specific proteases plasmepsin in vitro. A specific interaction between catestatin and plasmepsins II and IV from P. falciparum and plasmepsin IV from the three remaining species of Plasmodium known to infect man was observed, suggesting a catestatin-induced reduction in availability of nutrients for protein synthesis in the parasite.
Akaddar
Aziza
A
Institut de Parasitologie et de Pathologie Tropicale, Université de Strasbourg, France.
Doderer-Lang
Cécile
C
Marzahn
Melissa R
MR
Delalande
François
F
Mousli
Marc
M
Helle
Karen
K
Van Dorsselaer
Alain
A
Aunis
Dominique
D
Dunn
Ben M
BM
Metz-Boutigue
Marie-Hélène
MH
Candolfi
Ermanno
E
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors; D002417:Cattle; D053379:Chromogranin A / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development*; D013329:Structure-Activity Relationship
D053379:Chromogranin A; D010446:Peptide Fragments; C109084:chromogranin A (344-364); D007770:L-Lactate Dehydrogenase; D016282:Aspartic Acid Endopeptidases; C089643:plasmepsin