Journal
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
Volume 207, Issue 2, Pages 89-95Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.molbiopara.2016.06.005
Keywords
Leishmania; Glyoxalase pathway; Methylglyoxal; Inorganic phosphate; Glucose; Trivalent antimony
Categories
Funding
- Department of Biotechnology, Motilal Nehru National Institute of Technology Allahabad
Ask authors/readers for more resources
Similar to their mammalian counterpart, protozoan parasites including Leishmania donovani detoxify methylglyoxal (MG),(1) a toxic ubiquitous product generated in glycolysis pathway. However, it differs in one or more way(s) from the humans. It is known that MG is eliminated either through glyoxalase (GLO)(2) pathway and/or excreted across the cell membrane. This toxic metabolic by-product is known to be detoxified predominantly by the GLO pathway and excretion across the cell membrane is never considered to be a significant pathway for its detoxification. We have tried to modulate these pathways under various physiological conditions to find ways that may lead to accumulation of MG in L. donovani. Besides targeting the GLO pathway, we intend to understand the mechanism of MG release across the cell membrane and possible ways to inhibit its exclusion from parasites. In our study, it was found that inorganic phosphate (Pi)(3) in the presence of glucose inhibits the production of MG as well as promotes the expulsion of MG from the cell. Moreover, the trivalent form of antimony (Sb-III) inhibits GLO pathway and thus detoxification of MG. Inhibition of Pi transport, which is a Na+/H+ dependent process, restores the Pi mediated abrogation of MG production. Thus, Sb-III along with inhibitors of Pi transporter may be a therapeutic advancement for treatment of antimony resistant cases of human visceral leishmaniasis. However, it requires further validation using specific inhibitor(s) of Pi transporter. (C) 2016 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available