4.7 Article

Red blood cells contain enzymatically active GPx4 whose abundance anticorrelates with hemolysis during blood bank storage

期刊

REDOX BIOLOGY
卷 46, 期 -, 页码 -

出版社

ELSEVIER
DOI: 10.1016/j.redox.2021.102073

关键词

Red blood cells; GPx4; Blood storage

资金

  1. MSTP physician-scientist preceptorship via NIH MSTP [T32GM008692, 2UL 1TR000442, P01 CA217797, R01 CA169046, R01 GM073929]
  2. NIH [P30 ES005605, P42 ES013661]
  3. [P30 CA086862]

向作者/读者索取更多资源

The research revealed that GPx4 is an active enzyme in mature RBCs, protecting them from hemolysis during blood bank storage. It is correlated with lipid-anchored proteins and anti-correlated with lyso-phospholipids and complement system proteins.
The antioxidant function of the phospholipid hydroperoxide glutathione peroxidase (GPx4) is vital for the homeostasis of many cell types, from neoplastic cells to normal erythroid precursors. However, some functional proteins in erythroid precursors are lost during the development of red blood cells (RBCs); whether GPx4 is maintained as an active enzyme in mature RBCs has remained unclear. Our meta-analyses of existing RBC proteomics and metabolomics studies revealed the abundance of GPx4 to be correlated with lipid-anchored proteins. In addition, GPx4 anti-correlated with lyso-phospholipids and complement system proteins, further supporting the presence of active GPx4 in mature RBCs. To test the potential biological relevance of GPx4 in mature RBCs, we correlated the rate of hemolysis of human RBCs during storage with the abundance of GPx4 and other heritable RBC proteins. Of the molecules that anti-correlated with the rate of hemolysis of RBCs, proteins that mediate the cellular response to hydroperoxides, including GPx4, have the greatest enrichment. Western blotting further confirmed the presence of GPx4 antigenic protein in RBCs. Using an assay optimized to measure the activity of GPx4 in RBCs, we found GPx4 to be an active enzyme in mature RBCs, suggesting that GPx4 protects RBCs from hemolysis during blood bank storage.

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