Leishmania amazonensis META2 protein confers protection against heat shock and oxidative stress

TY - JOUR

T1 - Leishmania amazonensis META2 protein confers protection against heat shock and oxidative stress

AU - Ramos, Camila S.

AU - Yokoyama-Yasunaka, Jenicer K. U.

AU - Guerra-Giraldez, Cristina

AU - Price, Helen P.

AU - Mortara, Renato A.

AU - Smith, Deborah F.

AU - Uliana, Silvia R. B.

N1 - Copyright © 2010 Elsevier Inc. All rights reserved.

PY - 2011/1

Y1 - 2011/1

N2 - The META cluster of Leishmania amazonensis contains both META1 and META2 genes, which are upregulated in metacyclic promastigotes and encode proteins containing the META domain. Previous studies defined META2 as a 48.0-kDa protein, which is conserved in other Leishmania species and in Trypanosoma brucei. In this work, we demonstrate that META2 protein expression is regulated during the Leishmania life cycle but constitutive in T. brucei. META2 protein is present in the cytoplasm and flagellum of L amazonensis promastigotes. Leishmania META2-null replacement mutants are more sensitive to oxidative stress and, upon heat shock, assume rounded morphology with shortened flagella. The increased susceptibility of null parasites to heat shock is reversed by extra-chromosomal expression of the META2 gene. Defective Leishmania promastigotes exhibit decreased ability to survive in macrophages. By contrast, META2 expression is decreased by 80% in RNAi-induced T. brucei bloodstream forms with no measurable effect on survival or resistance to heat shock. (C) 2010 Elsevier Inc. All rights reserved.

AB - The META cluster of Leishmania amazonensis contains both META1 and META2 genes, which are upregulated in metacyclic promastigotes and encode proteins containing the META domain. Previous studies defined META2 as a 48.0-kDa protein, which is conserved in other Leishmania species and in Trypanosoma brucei. In this work, we demonstrate that META2 protein expression is regulated during the Leishmania life cycle but constitutive in T. brucei. META2 protein is present in the cytoplasm and flagellum of L amazonensis promastigotes. Leishmania META2-null replacement mutants are more sensitive to oxidative stress and, upon heat shock, assume rounded morphology with shortened flagella. The increased susceptibility of null parasites to heat shock is reversed by extra-chromosomal expression of the META2 gene. Defective Leishmania promastigotes exhibit decreased ability to survive in macrophages. By contrast, META2 expression is decreased by 80% in RNAi-induced T. brucei bloodstream forms with no measurable effect on survival or resistance to heat shock. (C) 2010 Elsevier Inc. All rights reserved.

KW - Animals

KW - Antiprotozoal Agents

KW - Blotting, Western

KW - Fluorescent Antibody Technique

KW - Gene Expression Regulation

KW - Hot Temperature

KW - Leishmania mexicana

KW - Leishmaniasis, Cutaneous

KW - Macrophages, Peritoneal

KW - Meglumine

KW - Mice

KW - Mice, Inbred BALB C

KW - Microscopy, Confocal

KW - Mutation

KW - Novobiocin

KW - Nucleic Acid Synthesis Inhibitors

KW - Organometallic Compounds

KW - Oxidative Stress

KW - Protozoan Proteins

KW - RNA Interference

KW - Recombinant Proteins

KW - Trypanosoma brucei brucei

UR - http://www.scopus.com/inward/record.url?scp=78650555999&partnerID=8YFLogxK

U2 - 10.1016/j.exppara.2010.08.004

DO - 10.1016/j.exppara.2010.08.004

M3 - Article

C2 - 20713053

SN - 0014-4894

VL - 127

SP - 228

EP - 237

JO - Experimental parasitology

JF - Experimental parasitology

IS - 1

ER -