The effect of TAO expression on PCD-like phenomenon development and drug resistance in Trypanosoma brucei.
Drug resistance in Trypanosoma brucei causes severe problems for people and domestic animals, but molecular mechanisms of the resistance are not well known. Programmed cell death (PCD) is a fundamental process in both multicellular and unicellular organisms, and it is speculated to be one of the important factors contributing to the emergence of drug resistance. We have previously reported that the expression of TAO appears to play a role in the inhibition of the PCD-like phenomenon development in T. brucei. In this study, to ascertain the correlation between the development of the PCD-like phenomenon and the expression of TAO in T. brucei, we genetically engineered T. brucei for conditional over-expression of the TAO gene. TAO over-expressing transgenic T. brucei was refractory to the development of the PCD-like phenomenon compared to the wild-type, indicating that expression of TAO might have a regulatory role on PCD development. Furthermore, the transgenic cells showed resistance to suramin and antrycide. We postulated that intracellular reactive oxygen species (ROS) may be involved in the mechanism of resistance to antrycide because augmentation of ROS in transgenic cells was lower than that in the wild-type cells following treatment with antrycide. These results suggest a possible correlation of PCD to drug resistance in T. brucei.
Tsuda
Akiko
A
Laboratory of Infectious Disease, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
Witola
William H
WH
Konnai
Satoru
S
Ohashi
Kazuhiko
K
Onuma
Misao
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D020287:In Situ Nick-End Labeling; D024101:Mitochondrial Proteins; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D021261:Parasitic Sensitivity Tests; D010940:Plant Proteins; D011806:Quinolinium Compounds / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology; D013997:Time Factors; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000201:enzymology; D014353:Trypanosomiasis, African / Q000188:drug therapy / Q000469:parasitology*; D000099188:Alternative Oxidase
D024101:Mitochondrial Proteins; D010088:Oxidoreductases; D010940:Plant Proteins; D011806:Quinolinium Compounds; D017382:Reactive Oxygen Species; D013498:Suramin; D014344:Trypanocidal Agents; D000099188:Alternative Oxidase; C005707:quinapyramine