Journal News

MCP: Predicting when blood goes bad

John Arnst
March 01, 2017

Despite the best efforts of blood banks and networks, some blood bags end up spoiling before they can make it to patients in need. A blood bag’s spoilage depends on the red blood cells’ ability to avoid hemolysis caused by low ATP levels. The breaking of red blood cells can release byproducts, such as iron and hemoglobin, that become toxic in a free-floating form by intensifying bacterial infections and interfering with the nitric oxide signaling that is key for vasodilation.

IMAGE COURTESY OF ERIN WEISENHORN

In a paper published in the journal Molecular & Cellular Proteomics, researchers at the University of Wisconsin–Madison have generated a model for predicting post-storage ATP levels in blood based on the concentrations of five key metabolic factors. They found these factors exhibited high heritability and were inherited as a block rather than individually.

“We can use this model to identify blood that can be potentially stored for longer or shorter periods as well as potentially identify other factors to make all blood store longer,” says Erin M. M. Weisenhorn. Weisenhorn, the first author on the paper, is a graduate student in Joshua J. Coon’s group.

To generate this model, the researchers performed a comprehensive metabolomics and proteomics study to examine heritability of metabolites associated with ATP consumption in the red blood cells in 18 pairs of twins. Heritability is the proportion of phenotypic variability due to genetic factors.

The researchers wanted to examine the proteins in the red blood cells’ membranes because of their high abundance there. To do this, they centrifuged the hemoglobin out of whole red blood cells, as it makes up about 98 percent of the cells’ protein content. The researchers digested the remaining proteins with trypsin and subjected them to a novel proteomics and metabolomics approach. The approach involved two sets of liquid chromatography with tandem mass spectrometry, separately optimized for acidic and basic metabolites, combined with a standard analysis by gas chromatography and mass spectrometry. They quantified 328 separate metabolites from the red blood cells, including those from the glycolysis and pentose phosphate pathway.

The researchers then identified 119 membrane proteins and 148 metabolite concentrations that had a heritability rate of more than 30 percent, which previously had been established as a benchmark level of heritability in studies with the same group of twins.

The researchers additionally found that there was a 60 to 90 percent chance of heritability for the entire set of metabolites related to the pathways. “We observe that you don’t just sort of randomly inherit high levels of 2, 3-diphosphoglycerate or pyruvate, but rather that the entire block of metabolites from the intermediate part of the pathway are all inherited at a higher or lower level,” says Thomas J. Raife, a co-author at the UW’s department of pathology and laboratory medicine. “This means a phenotype.”

The researchers proposed phenotypes for both high and low levels of ATP after six weeks of storage. The phenotypes correlated to five key parameters, which include pH and concentrations of phosphofructokinase, an essential enzyme in glycolysis, as well as the proteins Band 3, BPGM and CA1. As a trio, the latter proteins correlated negatively with post-storage ATP conditions, making lower concentrations desirable for blood viability.

This phenotypic existence of varying levels of glycolysis also could have implications for a variety of metabolic diseases, says Weisenhorn. One such correlation is the Warburg effect, in which a cancer is associated with extremely elevated levels of glycolysis. “You can potentially imagine if someone inherits higher levels of these glycolytic proteins or metabolites and has naturally higher flux through this pathway, then they might be more predisposed towards cancer.”

John Arnst

John Arnst is a science writer for ASBMB Today.

Join the ASBMB Today mailing list

Sign up to get updates on articles, interviews and events.

Latest in Science

Science highlights or most popular articles

A deeper insight into phospholipid biosynthesis in Gram-positive bacteria
Lipid News

A deeper insight into phospholipid biosynthesis in Gram-positive bacteria

February 18, 2020

Diego Sastre and Marcelo Guerin look at how membrane fluidity modulates the insertion of a peripheral enzyme to regulate bacterial phospholipid synthesis.

For vulnerable populations, the thorny ethics of genetic data collection
Feature

For vulnerable populations, the thorny ethics of genetic data collection

February 17, 2020

To be equitable, genetics research needs more diverse samples. But collecting that data could present ethical issues.

Anthrax vs. cancer
News

Anthrax vs. cancer

February 16, 2020

R. Claudio Aguilar explains how he joined forces with other labs in using a modified strain of anthrax to shrink tumors in dogs with terminal bladder cancer.

From the journals: JLR
Journal News

From the journals: JLR

February 11, 2020

Recent topics include interactions of the endocannabinoid pathway with the gut microbiome.

Selenium led Zhao from icy hometown to German hospitality
Award

Selenium led Zhao from icy hometown to German hospitality

February 09, 2020

JBC/Tabor award winner Wenchao Zhao studies Keshan disease, a nutrient deficiency named for the county in northeastern China where he grew up.

Dagar dissects a prostate cancer driver
Award

Dagar dissects a prostate cancer driver

February 08, 2020

This JBC/Tabor award winner has found a way to block androgen signaling in prostate cancer cells.