Intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins.

Malaria Journal
Piero BagnaresiMarcos L Gazarini

Abstract

The malaria burden remains a major public health concern, especially in sub-Saharan Africa. The complex biology of Plasmodium, the apicomplexan parasite responsible for this disease, challenges efforts to develop new strategies to control the disease. Proteolysis is a fundamental process in the metabolism of malaria parasites, but roles for proteases in generating vasoactive peptides have not previously been explored. In the present work, it was demonstrated by mass spectrometry analysis that Plasmodium parasites (Plasmodium chabaudi and Plasmodium falciparum) internalize and process plasma kininogen, thereby releasing vasoactive kinins (Lys-BK, BK and des-Arg9-BK) that may mediate haemodynamic alterations during acute malaria. In addition, it was demonstrated that the P. falciparum cysteine proteases falcipain-2 and falcipain-3 generated kinins after incubation with human kininogen, suggesting that these enzymes have an important role in this process. The biologic activity of peptides released by Plasmodium parasites was observed by measuring ileum contraction and activation of kinin receptors (B1 and B2) in HUVEC cells; the peptides elicited an increase in intracellular calcium, measured by Fluo-3 AM fluorescence. This effect...Continue Reading

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Citations

Feb 8, 2014·Molecular and Biochemical Parasitology·Pollyana M S MeloAdriana K Carmona
Oct 5, 2014·Analytical Biochemistry·Mayrim M GomesMarcos L Gazarini
Jul 20, 2016·Biochimica Et Biophysica Acta·Leandro de Souza SilvaAna Acacia Sá Pinheiro
Jun 27, 2019·Malaria Journal·Priscilla D S VenturaMarcos L Gazarini
Aug 28, 2020·Malaria Journal·Sarah El Chamy MalufAdriana Karaoglanovic Carmona
Sep 2, 2020·Pharmaceuticals·Ana Paula A DagninoRodrigo B M Silva
Mar 15, 2018·Frontiers in Immunology·Sonja Oehmcke-Hecht, Juliane Köhler
Jul 31, 2019·Journal of Medicinal Chemistry·Lorenzo CianniCarlos A Montanari

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Methods Mentioned

BETA
confocal microscopy

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