Journal
BLOOD ADVANCES
Volume 1, Issue 17, Pages 1296-1305Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/bloodadvances.2017007187
Keywords
-
Categories
Funding
- National Blood Foundation Early Career grant
- Boettcher WebbWaring Foundation Early Career Award
- National Institutes of Health (Office of the Director) [S10OD021641]
- University of Colorado Comprehensive Cancer Center Core Support (National Cancer Institute) [P30 CA046934-17]
- National Institute of General Medical Sciences [P50GM049222, T32GM008315, P50 GM049222]
Ask authors/readers for more resources
Red blood cells (RBCs) are the most abundant host cell in the human body and play a critical role inoxygen transport andsystemic metabolichomeostasis. Hypoxicmetabolic reprogramming of RBCs in response to high-altitude hypoxia or anaerobic storage in the blood bank has been extensively described. However, little is known about the RBC metabolism following hemorrhagic shock (HS), the most common preventable cause of death in trauma, the global leading cause of total life-years lost. Metabolomics analyses were performed through ultrahigh pressure liquid chromatography-mass spectrometry on RBCs from Sprague-Dawley rats undergoing HS (mean arterial pressure [MAP], <30 mm Hg) in comparison with sham rats (MAP,>80 mm Hg). Steady-state measurements were accompanied by metabolic flux analysis upon tracing of in vivo-injected (CN)-C-13-N-15-glutamine or inhibition of glutaminolysis using the anticancer drug CB-839. RBC metabolic phenotypes recapitulated the systemic metabolic reprogramming observed in plasma from the same rodent model. Results indicate that shock RBCs rely on glutamine to fuel glutathione (GSH) synthesis and pyruvate transamination, whereas abrogation of glutaminolysis conferred early mortality and exacerbated lactic acidosis and systemic accumulation of succinate, a predictor of mortality in the military and civilian critically ill populations. Glutamine is here identified as an essential amine group donor in HS RBCs, plasma, liver, and lungs, providing additional rationale for the central role glutaminolysis plays in metabolic reprogramming and survival following severe hemorrhage.
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