The Leishmania chagasi proteasome: role in promastigotes growth and amastigotes survival within murine macrophages

Acta Tropica
Izaltina Silva-JardimF Juarez Ramalho-Pinto

Abstract

Proteasomes are multisubunit proteases that exist universally among eukaryotes. They have multiple proteolytic activities and are believed to have important roles in regulating cell cycle, selective intracellular proteolysis, and antigen presentation. Here we have partially purified Leishmania chagasi proteasome. The L. chagasi proteasome rich fraction displayed the typical features of eukaryotic 20S proteasome complexes, being active towards peptidyl substrates with hydrophobic and acidic residues, and sensitive to the proteasome-specific inhibitor lactacystin. We have shown that lactacystin, or its active form clasto-lactacystin beta-lactone, but not E-64, blocks the in vitro growth of L. chagasi promastigotes, demonstrating that the interference with parasite growth is due to the lack of proteasome activity. Furthermore, pre-treatment of L. chagasi promastigotes with lactacystin did not prevent parasite entry in host cells, but markedly restricted its intracellular survival. These results demonstrate that intact parasite proteasome function is required for replication of L. chagasi and for amastigotes survival inside the vertebrate host cell.

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Citations

May 12, 2012·Asian Pacific Journal of Tropical Medicine·Nisha SinghRakesh Kumar Singh
Aug 5, 2011·Parasitology·Yolanda Pérez-PertejoRosa M Reguera
Jun 23, 2006·Proteomics·María Auxiliadora Dea-AyuelaFrancisco Bolás-Fernández
Jul 6, 2010·The International Journal of Biochemistry & Cell Biology·Juliano S ToledoAngela K Cruz
Jun 20, 2015·BioMed Research International·Christian MuñozJorge González
Dec 21, 2013·Bioorganic & Medicinal Chemistry·Nisha SinghVinod K Tiwari
May 15, 2007·Molecular and Biochemical Parasitology·Patricia CuervoElisa Cupolillo
Jan 26, 2017·The FEBS Journal·Betsaida Bibo-VerdugoAnthony J O'Donoghue
Nov 5, 2016·Revista Da Sociedade Brasileira De Medicina Tropical·Dionatas Ulises de Oliveira MeneguettiValdir Alves Facundo
Apr 19, 2017·Pharmaceutical Biology·Keline Medeiros de Araújo-VilgesSelma Aparecida Souza Kuckelhaus
May 3, 2018·Expert Opinion on Therapeutic Targets·Shyam Sundar, Bhawana Singh
May 10, 2020·Parasitology Research·Minelly Azevedo da SilvaChristian Collins Kuehn
Mar 19, 2021·Frontiers in Chemistry·Marie-José Bijlmakers

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