Partial biochemical characterization of a metalloproteinase from the bloodstream forms of Trypanosoma brucei brucei parasites.
Metalloproteinases (MMP) belong to the family of cation dependent endopeptidases that degrade matrices at physiological pH and to cleave extracellular matrix proteins. They play an important role in diverse physiological and pathological processes; not only there diverse types of MMP differ in structure and functionally, but also their enzymatic activity is regulated at multiple levels. Trying to shed some light over the processes that govern the pathology of African Trypanosomiasis, the aim of the present study was to examine the proteolytic activity of the crude trypanosome protein extract obtained from the bloodstream forms of Trypanosoma brucei brucei parasites. We hereby report the partial biochemical characterization of a neutral Trypanosoma brucei-metalloproteinase that displays marked proteolytic activities on gelatin and casein, with a molecular mass of approximately 40 kDa, whose activity is strongly dependent of pH and temperature. Furthermore, we show that this activity can be inhibited by classical MMP inhibitors such as EDTA, EGTA, phenantroline, and also by tetracycline and derivatives. This study has a relevant role in the search for new therapeutical targets, for the use of metalloproteinases inhibitors as treatment strategies, or as enhancement to trypanocidal drugs used in the treatment of the disease.
de Sousa
Karina Pires
KP
Unidade de Ensino e Investigação de Clínica das Doenças Tropicais, Centro de Malária e Outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Rua da Junqueira, Lisbon, Portugal.
Atouguia
Jorge
J
Silva
Marcelo Sousa
MS
D000818:Animals; D002852:Chromatography, Ion Exchange; D004792:Enzyme Precursors / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D045726:Metalloproteases / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D033761:Spores, Protozoan / Q000201:enzymology; D013696:Temperature; D014346:Trypanosoma brucei brucei / Q000201:enzymology*
D004792:Enzyme Precursors; D045726:Metalloproteases