Publication Date:
2022-05-25
Description:
Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Molecular and Biochemical Parasitology 167 (2009): 54-59, doi:10.1016/j.molbiopara.2009.04.007.
Description:
One potential physiological target for new antischistosomals is the parasite's system for excretion of wastes and xenobiotics. P-glycoprotein (Pgp), a member of the ATP-binding cassette superfamily of proteins, is an ATP-dependent efflux pump involved in transport of toxins and xenobiotics from cells. In vertebrates, increased expression of Pgp is associated with multidrug resistance in tumor cells. Pgp may also play a role in drug resistance in helminths. In this report, we examine the relationship between praziquantel (PZQ), the current drug of choice against schistosomiasis, and Pgp expression in Schistosoma mansoni. We show that levels of RNA for SMDR2, a Pgp homolog from S. mansoni, increase transiently in adult male worms following exposure to sublethal concentrations (100 - 500 nM) of PZQ. A corresponding, though delayed, increase in anti-Pgp immunoreactive protein expression occurs in adult males following exposure to PZQ. The level of anti-Pgp immunoreactivity in particular regions of adult worms also increases in response to PZQ. Adult worms from an Egyptian S. mansoni isolate with reduced sensitivity to PZQ express increased levels of SMDR2 RNA and anti-Pgp-immunoreactive protein, perhaps indicating a role for multidrug resistance proteins in development or maintenance of PZQ resistance.
Description:
SMM, RSK, WM, and RMG were supported by NIH grants R01 AI40522 and R01 AI 73660. RMG was also supported by the Neal Cornell Research Fund at the Marine Biological Laboratory. RMG and SMM were also supported in part by NIH/NSF Woods Hole Center for Oceans and Human Health grant WHOI-A100354/A100360. Support was also received from the NIH Biocurrents Research Center at MBL (P41 RR001395).
Keywords:
Schistosoma mansoni
;
P-glycoprotein
;
Multidrug resistance
;
Praziquantel
;
ABC transporter
Repository Name:
Woods Hole Open Access Server
Type:
Preprint
Format:
application/pdf
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