Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042961 (volvulus)
 4,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of oxidative insult on gene transcript levels in the filarial nematode Onchocerca volvulus were investigated using differential display RT-PCR. Oxidative stress was applied with the reagents paraquat, plumbagin and xanthine-xanthine oxidase. In all three cases, a cDNA fragment encoding a novel glutathione S-transferase (GST) resembling members of the theta-class was identified as upregulated (PQ29, PG112, XOD26). The subsequently isolated full-length cDNA harbors a 753-bp open reading frame encoding a GST with 268 amino acid residues and a predicted molecular mass of 31 kDa. This stress-responsive GST (Ov-GST-3) possesses only 14 and 21% sequence identity with the other O. volvulus GSTs (Ov-GST-1 and Ov-GST-2, respectively). Interestingly, Ov-GST-3 shares higher sequence identity with GSTs that are upregulated due to environmental stress. In order to confirm the specific upregulation of the Ov-GST-3 transcripts identified by differential display and to analyze the mRNA levels of the other Ov-GSTs (Ov-GST-1 and Ov-GST-2) under elevated stress conditions, a semi-quantitative polymerase chain reaction-enzyme-linked immunosorbent assay was performed. The Ov-GST-3 gene transcript level increased dramatically in response to xanthine-xanthine oxidase and to a lesser extent with paraquat and plumbagin. In contrast, Ov-GST-1 and Ov-GST-2 did not show any significant alterations in their steady-state mRNA levels in response to oxidative stress when examining the same mRNA samples. The present study clearly demonstrates that Ov-GST-3 is a critical enzyme in the defense against oxidative stress.
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PMID:Identification of a stress-responsive Onchocerca volvulus glutathione S-transferase (Ov-GST-3) by RT-PCR differential display. 1096 Jan 69

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.
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PMID:Functional analysis of the glutathione S-transferase 3 from Onchocerca volvulus (Ov-GST-3): a parasite GST confers increased resistance to oxidative stress in Caenorhabditis elegans. 1247 50