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Increase in Red Blood Cell-Nitric Oxide Synthase Dependent Nitric Oxide Production during Red Blood Cell Aging in Health and Disease: A Study on Age Dependent Changes of Rheologic and Enzymatic Properties in Red Blood Cells.
PLoS One. 2015; 10(4):e0125206.Plos

Abstract

AIM

To investigate RBC-NOS dependent NO signaling during in vivo RBC aging in health and disease.

METHOD

RBC from fifteen healthy volunteers (HC) and four patients with type 2 diabetes mellitus (DM) were separated in seven subpopulations by Percoll density gradient centrifugation.

RESULTS

The proportion of old RBC was significantly higher in DM compared to HC. In both groups, in vivo aging was marked by changes in RBC shape and decreased cell volume. RBC nitrite, as marker for NO, was higher in DM and increased in both HC and DM during aging. RBC deformability was lower in DM and significantly decreased in old compared to young RBC in both HC and DM. RBC-NOS Serine1177 phosphorylation, indicating enzyme activation, increased during aging in both HC and DM. Arginase I activity remained unchanged during aging in HC. In DM, arginase I activity was significantly higher in young RBC compared to HC but decreased during aging. In HC, concentration of L-arginine, the substrate of RBC-NOS and arginase I, significantly dropped from young to old RBC. In DM, L-arginine concentration was significantly higher in young RBC compared to HC and significantly decreased during aging. In blood from healthy subjects, RBC-NOS activation was additionally inhibited by N5-(1-iminoethyl)-L-Ornithine dihydrochloride which decreased RBC nitrite, and impaired RBC deformability of all but the oldest RBC subpopulation.

CONCLUSION

This study first-time showed highest RBC-NOS activation and NO production in old RBC, possibly to counteract the negative impact of cell shrinkage on RBC deformability. This was even more pronounced in DM. It is further suggested that highly produced NO only insufficiently affects cell function of old RBC maybe because of isolated RBC-NOS in old RBC thus decreasing NO bioavailability. Thus, increasing NO availability may improve RBC function and may extend cell life span in old RBC.

Links

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Authors+Show Affiliations

Bizjak DA
Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, Cologne, Germany.
Brinkmann C
Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, Cologne, Germany.
Bloch W
Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, Cologne, Germany.
Grau M
Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, Cologne, Germany.

MeSH

AdultArginaseBiomarkersCentrifugation, Density GradientDiabetes Mellitus, Type 2Enzyme InhibitorsErythrocyte AgingErythrocyte DeformabilityErythrocyte VolumeErythrocytesHealthHemorheologyHumansLinear ModelsMetabolomeNitric OxideNitric Oxide SynthaseNitritesOrnithinePhosphatidylserines

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25902315

Citation

Bizjak, Daniel Alexander, et al. "Increase in Red Blood Cell-Nitric Oxide Synthase Dependent Nitric Oxide Production During Red Blood Cell Aging in Health and Disease: a Study On Age Dependent Changes of Rheologic and Enzymatic Properties in Red Blood Cells." PloS One, vol. 10, no. 4, 2015, pp. e0125206.
Bizjak DA, Brinkmann C, Bloch W, et al. Increase in Red Blood Cell-Nitric Oxide Synthase Dependent Nitric Oxide Production during Red Blood Cell Aging in Health and Disease: A Study on Age Dependent Changes of Rheologic and Enzymatic Properties in Red Blood Cells. PLoS One. 2015;10(4):e0125206.
Bizjak, D. A., Brinkmann, C., Bloch, W., & Grau, M. (2015). Increase in Red Blood Cell-Nitric Oxide Synthase Dependent Nitric Oxide Production during Red Blood Cell Aging in Health and Disease: A Study on Age Dependent Changes of Rheologic and Enzymatic Properties in Red Blood Cells. PloS One, 10(4), e0125206. https://doi.org/10.1371/journal.pone.0125206
Bizjak DA, et al. Increase in Red Blood Cell-Nitric Oxide Synthase Dependent Nitric Oxide Production During Red Blood Cell Aging in Health and Disease: a Study On Age Dependent Changes of Rheologic and Enzymatic Properties in Red Blood Cells. PLoS One. 2015;10(4):e0125206. PubMed PMID: 25902315.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increase in Red Blood Cell-Nitric Oxide Synthase Dependent Nitric Oxide Production during Red Blood Cell Aging in Health and Disease: A Study on Age Dependent Changes of Rheologic and Enzymatic Properties in Red Blood Cells. AU - Bizjak,Daniel Alexander, AU - Brinkmann,Christian, AU - Bloch,Wilhelm, AU - Grau,Marijke, Y1 - 2015/04/22/ PY - 2014/12/17/received PY - 2015/03/11/accepted PY - 2015/4/23/entrez PY - 2015/4/23/pubmed PY - 2016/4/5/medline SP - e0125206 EP - e0125206 JF - PloS one JO - PLoS One VL - 10 IS - 4 N2 - AIM: To investigate RBC-NOS dependent NO signaling during in vivo RBC aging in health and disease. METHOD: RBC from fifteen healthy volunteers (HC) and four patients with type 2 diabetes mellitus (DM) were separated in seven subpopulations by Percoll density gradient centrifugation. RESULTS: The proportion of old RBC was significantly higher in DM compared to HC. In both groups, in vivo aging was marked by changes in RBC shape and decreased cell volume. RBC nitrite, as marker for NO, was higher in DM and increased in both HC and DM during aging. RBC deformability was lower in DM and significantly decreased in old compared to young RBC in both HC and DM. RBC-NOS Serine1177 phosphorylation, indicating enzyme activation, increased during aging in both HC and DM. Arginase I activity remained unchanged during aging in HC. In DM, arginase I activity was significantly higher in young RBC compared to HC but decreased during aging. In HC, concentration of L-arginine, the substrate of RBC-NOS and arginase I, significantly dropped from young to old RBC. In DM, L-arginine concentration was significantly higher in young RBC compared to HC and significantly decreased during aging. In blood from healthy subjects, RBC-NOS activation was additionally inhibited by N5-(1-iminoethyl)-L-Ornithine dihydrochloride which decreased RBC nitrite, and impaired RBC deformability of all but the oldest RBC subpopulation. CONCLUSION: This study first-time showed highest RBC-NOS activation and NO production in old RBC, possibly to counteract the negative impact of cell shrinkage on RBC deformability. This was even more pronounced in DM. It is further suggested that highly produced NO only insufficiently affects cell function of old RBC maybe because of isolated RBC-NOS in old RBC thus decreasing NO bioavailability. Thus, increasing NO availability may improve RBC function and may extend cell life span in old RBC. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/25902315/Increase_in_Red_Blood_Cell_Nitric_Oxide_Synthase_Dependent_Nitric_Oxide_Production_during_Red_Blood_Cell_Aging_in_Health_and_Disease:_A_Study_on_Age_Dependent_Changes_of_Rheologic_and_Enzymatic_Properties_in_Red_Blood_Cells_ DB - PRIME DP - Unbound Medicine ER -