Intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins
<p>Abstract</p> <p>Background</p> <p>The malaria burden remains a major public health concern, especially in sub-Saharan Africa. The complex biology of <it>Plasmodium</it>, the apicomplexan parasite responsible for this disease, challenges efforts to develop...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-05-01
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| Series: | Malaria Journal |
| Online Access: | http://www.malariajournal.com/content/11/1/156 |
| _version_ | 1811266318476771328 |
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| author | Bagnaresi Piero Barros Nilana MT Assis Diego M Melo Pollyana MS Fonseca Raphael G Juliano Maria A Pesquero João B Juliano Luiz Rosenthal Philip J Carmona Adriana K Gazarini Marcos L |
| author_facet | Bagnaresi Piero Barros Nilana MT Assis Diego M Melo Pollyana MS Fonseca Raphael G Juliano Maria A Pesquero João B Juliano Luiz Rosenthal Philip J Carmona Adriana K Gazarini Marcos L |
| author_sort | Bagnaresi Piero |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The malaria burden remains a major public health concern, especially in sub-Saharan Africa. The complex biology of <it>Plasmodium</it>, 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.</p> <p>Results</p> <p>In the present work, it was demonstrated by mass spectrometry analysis that <it>Plasmodium</it> parasites (<it>Plasmodium chabaudi</it> and <it>Plasmodium falciparum</it>) internalize and process plasma kininogen, thereby releasing vasoactive kinins (Lys-BK, BK and des-Arg<sup>9</sup>-BK) that may mediate haemodynamic alterations during acute malaria. In addition, it was demonstrated that the <it>P. falciparum</it> 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 <it>Plasmodium</it> 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 was suppressed by the specific receptor antagonists Des-Arg<sup>9</sup>[Leu<sup>8</sup>]-BK and HOE-140.</p> <p>Conclusions</p> <p>In previously undescribed means of modulating host physiology, it was demonstrated that malaria parasites can generate active kinins by proteolysis of plasma kininogen.</p> |
| first_indexed | 2024-04-12T20:39:58Z |
| format | Article |
| id | doaj.art-f69969934f994700bc1d4fc0aa78f858 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-04-12T20:39:58Z |
| publishDate | 2012-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-f69969934f994700bc1d4fc0aa78f8582022-12-22T03:17:27ZengBMCMalaria Journal1475-28752012-05-0111115610.1186/1475-2875-11-156Intracellular proteolysis of kininogen by malaria parasites promotes release of active kininsBagnaresi PieroBarros Nilana MTAssis Diego MMelo Pollyana MSFonseca Raphael GJuliano Maria APesquero João BJuliano LuizRosenthal Philip JCarmona Adriana KGazarini Marcos L<p>Abstract</p> <p>Background</p> <p>The malaria burden remains a major public health concern, especially in sub-Saharan Africa. The complex biology of <it>Plasmodium</it>, 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.</p> <p>Results</p> <p>In the present work, it was demonstrated by mass spectrometry analysis that <it>Plasmodium</it> parasites (<it>Plasmodium chabaudi</it> and <it>Plasmodium falciparum</it>) internalize and process plasma kininogen, thereby releasing vasoactive kinins (Lys-BK, BK and des-Arg<sup>9</sup>-BK) that may mediate haemodynamic alterations during acute malaria. In addition, it was demonstrated that the <it>P. falciparum</it> 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 <it>Plasmodium</it> 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 was suppressed by the specific receptor antagonists Des-Arg<sup>9</sup>[Leu<sup>8</sup>]-BK and HOE-140.</p> <p>Conclusions</p> <p>In previously undescribed means of modulating host physiology, it was demonstrated that malaria parasites can generate active kinins by proteolysis of plasma kininogen.</p>http://www.malariajournal.com/content/11/1/156 |
| spellingShingle | Bagnaresi Piero Barros Nilana MT Assis Diego M Melo Pollyana MS Fonseca Raphael G Juliano Maria A Pesquero João B Juliano Luiz Rosenthal Philip J Carmona Adriana K Gazarini Marcos L Intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins Malaria Journal |
| title | Intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins |
| title_full | Intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins |
| title_fullStr | Intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins |
| title_full_unstemmed | Intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins |
| title_short | Intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins |
| title_sort | intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins |
| url | http://www.malariajournal.com/content/11/1/156 |
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