The effect of TAO expression on PCD-like phenomenon development and drug resistance in Trypanosoma brucei

Akiko Tsuda, William H. Witola, Satoru Konnai, Kazuhiko Ohashi, Misao Onuma

Research output: Research - peer-reviewArticle

Abstract

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.

LanguageEnglish (US)
Pages135-142
Number of pages8
JournalParasitology International
Volume55
Issue number2
DOIs
StatePublished - Jun 2006
Externally publishedYes

Fingerprint

Troleandomycin
Trypanosoma brucei brucei
Drug Resistance
Cell Death
quinapyramine
Reactive Oxygen Species
Suramin
Domestic Animals
Gene Expression

Keywords

  • Antrycide
  • Drug resistance
  • Programmed cell death
  • Suramin
  • Trypanosoma brucei
  • Trypanosome alternative oxidase

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

The effect of TAO expression on PCD-like phenomenon development and drug resistance in Trypanosoma brucei. / Tsuda, Akiko; Witola, William H.; Konnai, Satoru; Ohashi, Kazuhiko; Onuma, Misao.

In: Parasitology International, Vol. 55, No. 2, 06.2006, p. 135-142.

Research output: Research - peer-reviewArticle

Tsuda, Akiko ; Witola, William H. ; Konnai, Satoru ; Ohashi, Kazuhiko ; Onuma, Misao. / The effect of TAO expression on PCD-like phenomenon development and drug resistance in Trypanosoma brucei. In: Parasitology International. 2006 ; Vol. 55, No. 2. pp. 135-142
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