Journal article
Heritability of glutathione and related metabolites in stored red blood cells
Free radical biology & medicine, Vol.76, pp.107-113
11/2014
DOI: 10.1016/j.freeradbiomed.2014.07.040
PMCID: PMC4252477
PMID: 25108189
Abstract
Red blood cells (RBCs) collected for transfusion deteriorate during storage. This deterioration is termed the "RBC storage lesion." There is increasing concern over the safety, therapeutic efficacy, and toxicity of transfusing longer-stored units of blood. The severity of the RBC storage lesion is dependent on storage time and varies markedly between individuals. Oxidative damage is considered a significant factor in the development of the RBC storage lesion. In this study, the variability during storage and heritability of antioxidants and metabolites central to RBC integrity and function were investigated. In a classic twin study, we determined the heritability of glutathione (GSH), glutathione disulfide (GSSG), the status of the GSSG,2H(+)/2GSH couple (Ehc), and total glutathione (tGSH) in donated RBCs over 56 days of storage. Intracellular GSH and GSSG concentrations both decrease during storage (median net loss of 0.52 ± 0.63 mM (median ± SD) and 0.032 ± 0.107 mM, respectively, over 42 days). Taking into account the decline in pH, Ehc became more positive (oxidized) during storage (median net increase of 35 ± 16 mV). In our study population heritability estimates for GSH, GSSG, tGSH, and Ehc measured over 56 days of storage are 79, 60, 67, and, 75%, respectively. We conclude that susceptibility of stored RBCs to oxidative injury due to variations in the GSH redox buffer is highly variable among individual donors and strongly heritable. Identifying the genes that regulate the storage-related changes in this redox buffer could lead to the development of new methods to minimize the RBC storage lesion.
Details
- Title: Subtitle
- Heritability of glutathione and related metabolites in stored red blood cells
- Creators
- Thomas J van 't Erve - Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA 52242, USAClaire M Doskey - Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA 52242, USABrett A Wagner - Free Radical and Radiation Biology Program, Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USAJohn R Hess - Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USABenjamin W Darbro - Department of Pediatrics, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAKelli K Ryckman - Department of Epidemiology, College of Public Health, The University of Iowa, Iowa City, IA 52242, USAJeffrey C Murray - Department of Pathology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAThomas J Raife - Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242, USAGarry R Buettner - Free Radical and Radiation Biology Program, Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USA; Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242, USA. Electronic address: garry-buettner@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Free radical biology & medicine, Vol.76, pp.107-113
- DOI
- 10.1016/j.freeradbiomed.2014.07.040
- PMID
- 25108189
- PMCID
- PMC4252477
- NLM abbreviation
- Free Radic Biol Med
- ISSN
- 1873-4596
- eISSN
- 1873-4596
- Publisher
- United States
- Grant note
- P30 ES005605 / NIEHS NIH HHS R01 GM073929 / NIGMS NIH HHS P01HL046925 / NHLBI NIH HHS P42 ES013661 / NIEHS NIH HHS R01GM073929 / NIGMS NIH HHS P01 HL046925 / NHLBI NIH HHS P42ES013661 / NIEHS NIH HHS UL1 TR000442 / NCATS NIH HHS P30 CA086862 / NCI NIH HHS R01 CA169046 / NCI NIH HHS R01CA169046 / NCI NIH HHS 2UL1TR000442-06 / NCATS NIH HHS P30ES005605 / NIEHS NIH HHS P30CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 11/2014
- Academic Unit
- Anatomy and Cell Biology; International Programs; Stead Family Department of Pediatrics; Epidemiology; Medical Genetics and Genomics; Pediatric Dentistry; Radiation Oncology; Craniofacial Anomalies Research Center; Nursing; Public Policy Center (Archive); Dental Research
- Record Identifier
- 9983995039502771
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