Divergence of trypanothione-dependent tryparedoxin cascade into cytosolic and mitochondrial pathways in arsenite-resistant variants of Leishmania amazonensis.
Evidences are presented in the in vivo study that overexpression of tryparedoxin peroxidases (TXNPxs) diverged into cytosolic pathway in arsenite-resistant variant A and mitochondrial pathway in variant A' of Leishmania amazonensis is due to the upregulation of the corresponding upstream tryparedoxins (TXNs) in the cytosol as well as the mitochondrion respectively. Evidences are also presented that exposure of L. amazonensis to arsenite in the early hours led to the production of reactive oxygen species (ROS), which in turn induced the overexpression of the genes of both cytosolic and mitochondrial trypanothione-dependent tryparedoxin pathway due probably to physiological and functional needs. The sequence of events leading to the upregulation indicates that cytosolic tryparedoxin pathway is upregulated earlier than that of mitochondrial tryparedoxin pathway. Based on the kinetics of gene upregulation of the cytosolic pathway is different from that of mitochondrial pathway, and cTXNPx and mTXNPx differentially detoxify H(2)O(2) and of t-butyl hydroperoxide respectively, it is postulated that during arsenite selection, different ROS species may have been overproduced in either variants A or A', leading to the divergence of the trypanothione-dependent tryparedoxin pathways in these variants.
Hsu
Ju-Yu
JY
Division of Infectious Diseases, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC.
Lin
Yi-Chun
YC
Chiang
Su-Chi
SC
Lee
Sho Tone
ST
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D018053:Arsenites / Q000494:pharmacology*; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004352:Drug Resistance, Microbial; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007891:Leishmania / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013095:Spermidine / Q000031:analogs & derivatives* / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism*; D020122:tert-Butylhydroperoxide / Q000378:metabolism
D000981:Antiprotozoal Agents; D018053:Arsenites; D016054:DNA, Protozoan; D015800:Protozoan Proteins; D017382:Reactive Oxygen Species; C114110:tryparedoxin; D013879:Thioredoxins; D020122:tert-Butylhydroperoxide; C044809:trypanothione; D006861:Hydrogen Peroxide; D005978:Glutathione; C015001:arsenite; D013095:Spermidine