Inhibition of Setaria cervi protein tyrosine phosphatases by Phenylarsine oxide: A proteomic and biochemical study

Singh, Neetu; Wadhawan, Mohit; Tiwari, Savitri; Kumar, Ranjeet; Rathaur, Sushma

doi:10.1016/j.actatropica.2016.03.004

Cited by 10 publications

(5 citation statements)

References 47 publications

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“…In fact, PAO is a protein phosphatase inhibitor [24] and contains a phenyl group. Thus, we hypothesized that inhibition of protein phosphatase activity or phenyl group of PAO may be involved in PML protein solubility changes.…”

Section: Resultsmentioning

confidence: 99%

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Phenylarsine Oxide Can Induce the Arsenite-Resistance Mutant PML Protein Solubility Changes

Jiang

Chen

Wang

et al. 2017

IJMS

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Arsenic trioxide (As2O3) has recently become one of the most effective drugs for treatment of patient with acute promyelocytic leukemia (APL), and its molecular mechanism has also been largely investigated. However, it has been reported that As2O3 resistant patients are frequently found in relapsed APL after consolidation therapy, which is due to the point mutations in B-box type 2 motifs of promyelocytic leukemia (PML) gene. In the present study, we for the first time establish whether organic arsenic species phenylarsine oxide (PAO) could induce the mutant PML-IV (A216V) protein solubility changes and degradation. Here, three different PML protein variants (i.e., PML-IV, PML-V and mutant PML-A216V) were overexpressed in HEK293T cells and then exposed to PAO in time- and dose-dependent manners. Interestingly, PAO is found to have potential effect on induction of mutant PML-IV (A216V) protein solubility changes and degradation, but no appreciable effects were found following exposure to high concentrations of iAsIII, dimethylarsinous acid (DMAIII) and adriamycin (doxorubicin), even though they cause cell death. Our current data strongly indicate that PAO has good effects on the mutant PML protein solubility changes, and it may be helpful for improving the therapeutic strategies for arsenic-resistant APL treatments in the near future.

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Section: Resultsmentioning

confidence: 99%

“…Phenylarsine oxide (PAO) is a membrane-permeable protein-tyrosine phosphatase (PTPase) inhibitor [24]. An report has indicated that PAO is capable of inhibiting proliferation or inducing apoptosis of AML cells in vitro [27].…”

Section: Discussionmentioning

confidence: 99%

Phenylarsine Oxide Can Induce the Arsenite-Resistance Mutant PML Protein Solubility Changes

Jiang

Chen

Wang

et al. 2017

IJMS

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“…For COX activity, the mitochondrial fractions were extracted from the control and treated parasites according to the protocol given by Ericson et al (2012). The calpain activity was measured according to our lab's standardized protocol (Singh et al, 2016). Caspase-3 activity was measured in control and treated worm extracts by a colorimetric assay (Schroeter et al, 2001).…”

Section: Measurement Of Apoptotic Markersmentioning

confidence: 99%

“…Filarial worms possess a strong antioxidant system which plays important role in their long persistence within the host (Singh et al, 2016). According to WHO prescribed antifilarial drugs are not 100% effective in killing adult worms.…”

Section: Introductionmentioning

confidence: 99%

The HSP90 inhibitor 17‐AAG induced calcium‐mediated apoptosis in filarial parasites

Ahmad

Sharma

Yadav

et al. 2022

Drug Development Research

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The available antifilarial medications are effective only against the larval stage of the filarial parasite. As a result, there is a pressing need for an adulticidal drug.The development of drugs requires the identification of molecular targets that are critical for parasite life. In this study, we observed the effect of 17-N-allyl-17demethoxygeldanamycin on the survival of adult filarial parasites. The 17-N-allyl-17demethoxygeldanamycin (17-AAG) is a derivative of geldanamycin (GA), which is an inhibitor of heat shock protein (HSP)90. It is less toxic as compared to geldanamycin. The motility and viability of the adult filarial parasite Setaria cervi were decreased on exposure to 17-AAG at 2.5 and 5.0 μM/ml concentrations. The 17-AAG treated parasites showed induction of oxidative stress as evidenced by decreased activity of various antioxidant enzymes like glutathione s-transferase, glutathione reductase, thioredoxin reductase, and an increase in ROS production in comparison to control. Oxidative stress may lead to altered calcium homeostasis. Indeed, in 17-AAG treated worms, there was a rise in calcium in the cytosol and mitochondria, as well as a decrease in the ER. We also observed enhanced activity of phospholipase C in the treated parasite, suggesting the opening of calcium channels located on the ER membrane. ER stress is marked by a reduced level of protein disulfide isomerase. Further, 17-AAG treated worms showed an increase in apoptotic marker enzyme activities like calpain, cyt-c, and caspase-3. The 2Dgel electrophoresis technique showed 142 protein spots in the control and 112 spots in the 17-AAG treated parasite. Thus, 17-AAG induced oxidative stress, and altered calcium, and proteostasis of parasites, which led to apoptosis.

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“…acute promyelocytic leukaemia (Wang 2001), human hepatocellular carcinoma (Huang et al 2017) or lung cancer (Huang and Zeng 2019)). In addition to treating cancer, As compounds are also used to treat parasitic diseases caused by Trypanosoma brucei (Mandal et al 2013), Leishmania donovani (Mehta and Shaha 2006) and Setaria cervi (Singh et al 2016), among others. During treatment, relatively high doses are administered over a long period of time, with dosages ranging from 0.15 to 0.25 mg/kg of As 2 O 3 per day, for 5-6 weeks (Liu et al 2006;Subbarayan et al 2007;Platzbecker et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Controlled preparation of arsenic nanoparticles

2021

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Inhibition of Setaria cervi protein tyrosine phosphatases by Phenylarsine oxide: A proteomic and biochemical study

Cited by 10 publications

References 47 publications

Phenylarsine Oxide Can Induce the Arsenite-Resistance Mutant PML Protein Solubility Changes

Phenylarsine Oxide Can Induce the Arsenite-Resistance Mutant PML Protein Solubility Changes

The HSP90 inhibitor 17‐AAG induced calcium‐mediated apoptosis in filarial parasites

Controlled preparation of arsenic nanoparticles

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