title: Inhibition of Setaria cervi protein tyrosine phosphatases by Phenylarsine oxide: A proteomic and biochemical study.
abstract: Phenylarsine oxide (PAO), a specific protein tyrosine phosphatase (PTP) inhibitor significantly decreased the motility and viability of Setaria cervi ultimately leading to its death. The PTP activity present in the cytosolic and detergent soluble fractions as well as on surface of these parasites was significantly inhibited by PAO. A marked alteration in protein spots abundance after proteomic analysis showed 14 down-regulated and 9 upregulated spots in the treated parasites as compared to the control. The PTP inhibition led to increase in the cytosolic and mitochondrial calpain activity in these parasites. PAO also blocked the ATP generation in the parasite depicted by reduced activity of phosphoglycerate kinase and expression of enolase. An increased ROS level, induced lipid peroxidation/protein carbonyl formation and decreased activity of different antioxidant enzymes like thioredoxin reductase, glutathione reductase and glutathione transferases was also observed in the PAO treated parasites. PAO, thus disturbs the overall homeostasis of the filarial parasite by inhibiting PTPs. Thereby suggesting that these molecules could be used as a good chemotherapeutic target for lymphatic filariasis.
authors.affiliation: Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Neetu
authors.initials: N
authors.lastname: Singh
authors.affiliation: Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Mohit
authors.initials: M
authors.lastname: Wadhawan
authors.affiliation: Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Savitri
authors.initials: S
authors.lastname: Tiwari
authors.affiliation: Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Ranjeet
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India. Electronic address: surathaur@rediffmail.com.
authors.forename: Sushma
authors.initials: S
authors.lastname: Rathaur
mesh_terms: D000818:Animals; D001152:Arsenicals / Q000378:metabolism*; D002020:Buffaloes / Q000469:parasitology; D004791:Enzyme Inhibitors / Q000378:metabolism*; D015801:Helminth Proteins / Q000378:metabolism*; D007194:India; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D040901:Proteomics; D017182:Setaria Nematode / Q000201:enzymology*; D012719:Setariasis / Q000469:parasitology* / Q000517:prevention & control*
chemical_list: D001152:Arsenicals; D004791:Enzyme Inhibitors; D015801:Helminth Proteins; C029341:oxophenylarsine; D017027:Protein Tyrosine Phosphatases
keywords: Lymphatic filariasis; Necrosis; Oxidative stress; Phenylarsine oxide; Protein tyrosine phosphatases