Summary of Study ST001864

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001177. The data can be accessed directly via it's Project DOI: 10.21228/M8K41X This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

Study ID	ST001864
Study Title	Targeting host glycolysis as a strategy for antimalarial development
Study Summary	Glycolysis controls cellular energy, redox balance, and biosynthesis. Antiglycolytic therapies are under investigation for treatment of obesity, cancer, aging, autoimmunity, and microbial diseases. Interrupting glycolysis is highly valued as a therapeutic strategy, because glycolytic disruption is generally tolerated in mammals. Unfortunately, anemia is a known dose-limiting side effect of these inhibitors and presents a major caveat to development of antiglycolytic therapies. We developed specific inhibitors of enolase – a critical enzyme in glycolysis – and validated their metabolic and cellular effects on human erythrocytes. Enolase inhibition increases erythrocyte susceptibility to oxidative damage and induces rapid and premature erythrocyte senescence, rather than direct hemolysis. We apply our model of red cell toxicity to address questions regarding erythrocyte glycolytic disruption in the context of Plasmodium falciparum malaria pathogenesis. Our study provides a framework for understanding red blood cell homeostasis under normal and disease states and clarifies the importance of erythrocyte reductive capacity in malaria parasite growth.
Institute	University of Colorado Anschutz Medical Campus
Last Name	Haines
First Name	Julie
Address	12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA
Email	julie.haines@cuanschutz.edu
Phone	3037243339
Submit Date	2021-07-02
Raw Data Available	Yes
Raw Data File Type(s)	raw(Thermo)
Analysis Type Detail	LC-MS
Release Date	2021-07-24
Release Version	1

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Treatment:

Treatment ID:	TR001953
Treatment Summary:	Freshly collected erythrocytes were washed, resuspended to 10% hematocrit in buffer [25mM HEPES (pH 7.4), 120mM NaCl, 5.4mM KCl, 1.8mM CaCl2, and 1mM NaH2PO4], incubated for 1 hour at 37ºC, then centrifuged at 2000xg for 5 minutes at 4ºC, resuspended in fresh wash buffer to 30-40% hematocrit, and split into 210uL aliquots of packed erythrocytes. Erythrocytes were resuspended in 253uL of RPMI containing 11.9mM D-[1,2,3-13C] glucose (Millipore-Sigma) and either treated with POM-SF or POM-HEX at five times the EC50s for MetHb formation, or an untreated solvent control with the balance volume to 550uL using washing buffer. All samples were incubated at 37ºC shaking at 500 RPM. Triplicate samples of supernatants and packed erythrocytes were collected at 0, 0.5, 1, and 6-hour intervals and snap-frozen in liquid N2.

Treatment ID:

TR001953

Treatment Summary:

Freshly collected erythrocytes were washed, resuspended to 10% hematocrit in buffer [25mM HEPES (pH 7.4), 120mM NaCl, 5.4mM KCl, 1.8mM CaCl2, and 1mM NaH2PO4], incubated for 1 hour at 37ºC, then centrifuged at 2000xg for 5 minutes at 4ºC, resuspended in fresh wash buffer to 30-40% hematocrit, and split into 210uL aliquots of packed erythrocytes. Erythrocytes were resuspended in 253uL of RPMI containing 11.9mM D-[1,2,3-13C] glucose (Millipore-Sigma) and either treated with POM-SF or POM-HEX at five times the EC50s for MetHb formation, or an untreated solvent control with the balance volume to 550uL using washing buffer. All samples were incubated at 37ºC shaking at 500 RPM. Triplicate samples of supernatants and packed erythrocytes were collected at 0, 0.5, 1, and 6-hour intervals and snap-frozen in liquid N2.