Molecular events leading to death of Leishmania donovani under spermidine starvation after hypericin treatment

Chemical Biology & Drug Design
Shalini SinghVikash Kumar Dubey

Abstract

We have previously reported that the hypericin treatment caused spermidine starvation and death of Leishmania parasite. Here, we report different molecular events under spermidine starvation and potential role of spermidine in processes other than redox homeostasis of the parasite. We have analyzed changes in expression of several genes by using quantitative gene expression analysis. Further, these changes at molecular level were also confirmed by using biochemical and cellular studies. Altered expression of several genes involved in redox metabolism, hypusine modification of eIF5A, DNA repair pathway and autophagy was observed. There was decrease in Sir2RP expression after hypericin treatment and this decrease has been found to be associated with induced ROS due to hypericin treatment as it has been rescued by either trypanothione or spermidine supplementation. Translation initiation in the parasite was decreased upon spermidine starvation. We also observed increased AMPK expression upon hypericin treatment. The increase in intracellular ATP and NAD(+) levels as well as decrease in Sir2RP expression of the parasite are cytoprotective mechanism towards generated ROS due to hypericin treatment possibly by inducing autophagy as i...Continue Reading

References

Sep 23, 1997·BioTechniques·J Liao, Z Gong
Oct 29, 2003·Trends in Parasitology·Simon L Croft, Graham H Coombs
Apr 30, 2005·Nucleic Acids Research·Yoav AravaDaniel Herschlag
Nov 1, 2005·Lancet·Henry W MurrayNancy G Saravia
May 3, 2008·Proceedings of the National Academy of Sciences of the United States of America·Manas K ChattopadhyayHerbert Tabor
May 9, 2009·Nature·Preeti SainiThomas E Dever
Sep 17, 2009·Applied Biochemistry and Biotechnology·Anil Kumar ShuklaVikash Kumar Dubey
Oct 6, 2009·Nature Cell Biology·Tobias EisenbergFrank Madeo
Jan 30, 2010·Autophagy·Frank MadeoGuido Kroemer
Oct 12, 2010·Trends in Biochemical Sciences·Kun-Liang Guan, Yue Xiong
Jan 8, 2011·BMC Research Notes·Lucélia TavaresClaudia N Santos
Jan 25, 2011·Nature Cell Biology·Joungmok KimKun-Liang Guan
Jun 27, 2012·Autophagy·Cong Yi, Li Yu
Jan 25, 2013·Proceedings of the National Academy of Sciences of the United States of America·Swati MandalMyung Hee Park
Aug 10, 2013·Mutation Research·Fade Gong, Kyle M Miller
Sep 5, 2013·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Prakash SaudagarVikash Kumar Dubey
Jan 15, 2014·The American Journal of Tropical Medicine and Hygiene·Prakash Saudagar, Vikash Kumar Dubey
Jul 18, 2014·Critical Reviews in Biochemistry and Molecular Biology·Thomas E DeverByung-Sik Shin
Apr 29, 2016·PloS One·Shalini Singh, Vikash Kumar Dubey

❮ Previous
Next ❯

Citations

Jun 4, 2019·Frontiers in Psychiatry·Nils C Gassen, Theo Rein

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autophagy & Metabolism

Autophagy preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones. In starvation, it provides an internal source of nutrients for energy generation and, thus, survival. A powerful promoter of metabolic homeostasis at both the cellular and whole-animal level, autophagy prevents degenerative diseases. It does have a downside, however--cancer cells exploit it to survive in nutrient-poor tumors.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms