期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 325, 期 1, 页码 25-37出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/S0022-2836(02)01174-9
关键词
transgenic Caenorhabditis elegans; Onchocerca volvulus; glutathione S-transferase; reactive oxygen species; stress resistance
This study examined the genomic organisation of the coding region of the glutathione S-transferase 3 (Ov-GST-3) from the human parasitic nematode Onchocerca volvulus; alternative splicing leads to three different transcripts (Ov-GST-3/1; Ov-GST-3/2 and Ov-GST-3/3). Since the expression of Ov-GST-3 is inducible by oxidative stress, it is assumed that it is involved in the defense against reactive oxygen species (ROS) resulting from cellular metabolism. Furthermore, we suggest that Ov-GST-3 plays an important role in the protection of the parasite against ROS derived from the host's immune system. To experimentally investigate these speculations, we generated Caenorhabditis elegans lines transgenic for Ov-GST-3 (AK1) and examined their resistance to artificially generated ROS. The AK1 worms (extrachromosomal and integrated lines) were found to be much more resistant to internal (juglone) and external (hypoxanthine/xanthine oxidase) oxidative stress than wild-type C. elegans worms. RNA interference experiments targeted to the Ov-GST-3 transcripts resulted in decreased resistance, confirming that this effect is due to the transgenic expression of Ov-GST-3. These results clearly demonstrate that the Ov-GST-3 gene confers an increased resistance to oxidative stress. This study also shows the applicability of C. elegans as a model organism for the functional characterization of genes from (parasitic) nematode species which are not accessible to genetic manipulations. (C) 2002 Elsevier Science Ltd. All rights reserved.
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