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Erythrocyte ion content and dehydration modulate maximal Gardos channel activity in KCNN4 V282M/+ hereditary xerocytosis red cells.
Rivera, A, Vandorpe, DH, Shmukler, BE, Andolfo, I, Iolascon, A, Archer, NM, Shabani, E, Auerbach, M, Hamerschlak, N, Morton, J, et al
American journal of physiology. Cell physiology. 2019;(2):C287-C302
Abstract
Hereditary xerocytosis (HX) is caused by missense mutations in either the mechanosensitive cation channel PIEZO1 or the Ca2+-activated K+ channel KCNN4. All HX-associated KCNN4 mutants studied to date have revealed increased current magnitude and red cell dehydration. Baseline KCNN4 activity was increased in HX red cells heterozygous for KCNN4 mutant V282M. However, HX red cells maximally stimulated by Ca2+ ionophore A23187 or by PMCA Ca2+-ATPase inhibitor orthovanadate displayed paradoxically reduced KCNN4 activity. This reduced Ca2+-stimulated mutant KCNN4 activity in HX red cells was associated with unchanged sensitivity to KCNN4 inhibitor senicapoc and KCNN4 activator Ca2+, with slightly elevated Ca2+ uptake and reduced PMCA activity, and with decreased KCNN4 activation by calpain inhibitor PD150606. The altered intracellular monovalent cation content of HX red cells prompted experimental nystatin manipulation of red cell Na and K contents. Nystatin-mediated reduction of intracellular K+ with corresponding increase in intracellular Na+ in wild-type cells to mimic conditions of HX greatly suppressed vanadate-stimulated and A23187-stimulated KCNN4 activity in those wild-type cells. However, conferral of wild-type cation contents on HX red cells failed to restore wild-type-stimulated KCNN4 activity to those HX cells. The phenotype of reduced, maximally stimulated KCNN4 activity was shared by HX erythrocytes expressing heterozygous PIEZO1 mutants R2488Q and V598M, but not by HX erythrocytes expressing heterozygous KCNN4 mutant R352H or PIEZO1 mutant R2456H. Our data suggest that chronic KCNN4-driven red cell dehydration and intracellular cation imbalance can lead to reduced KCNN4 activity in HX and wild-type red cells.
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The diagnostic and prognostic value of red cell distribution width in cardiovascular disease; current status and prospective.
Parizadeh, SM, Jafarzadeh-Esfehani, R, Bahreyni, A, Ghandehari, M, Shafiee, M, Rahmani, F, Parizadeh, MR, Seifi, S, Ghayour-Mobarhan, M, Ferns, GA, et al
BioFactors (Oxford, England). 2019;(4):507-516
Abstract
The red blood cell distribution width (RDW) is an index of the heterogeneity of circulating red blood cell size, which along with other standard complete blood count (CBC) parameters are used to identify hematological system diseases. Besides hematological disorders, several clinical studies have shown that an increased in the RDW may be associated with other diseases including acute pancreatitis, chronic kidney disease, gastrointestinal disorders, cancer, and of special interest in this review, cardiovascular disease (CVD). The diagnostic and prognostic value of RDW in different CVD (acute coronary syndrome, ischemic cerebrovascular disease, peripheral artery disease, atrial fibrillation, heart failure, and acute ischemic stroke) has been reviewed in this article, to provide an understanding how its measurement may be applied to improve the management of these conditions.
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Defining the plasma folate concentration associated with the red blood cell folate concentration threshold for optimal neural tube defects prevention: a population-based, randomized trial of folic acid supplementation.
Chen, MY, Rose, CE, Qi, YP, Williams, JL, Yeung, LF, Berry, RJ, Hao, L, Cannon, MJ, Crider, KS
The American journal of clinical nutrition. 2019;(5):1452-1461
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Abstract
BACKGROUND For women of reproductive age, a population-level red blood cell (RBC) folate concentration below the threshold 906 nmol/L or 400 ng/mL indicates folate insufficiency and suboptimal neural tube defect (NTD) prevention. A corresponding population plasma/serum folate concentration threshold for optimal NTD prevention has not been established. OBJECTIVE The aim of this study was to examine the association between plasma and RBC folate concentrations and estimated a population plasma folate insufficiency threshold (pf-IT) corresponding to the RBC folate insufficiency threshold (RBCf-IT) of 906 nmol/L. METHODS We analyzed data on women of reproductive age (n = 1673) who participated in a population-based, randomized folic acid supplementation trial in northern China. Of these women, 565 women with anemia and/or vitamin B-12 deficiency were ineligible for folic acid intervention (nonintervention group); the other 1108 received folic acid supplementation for 6 mo (intervention group). We developed a Bayesian linear model to estimate the pf-IT corresponding to RBCf-IT by time from supplementation initiation, folic acid dosage, methyltetrahydrofolate reductase (MTHFR) genotype, body mass index (BMI), vitamin B-12 status, or anemia status. RESULTS Using plasma and RBC folate concentrations of the intervention group, the estimated median pf-IT was 25.5 nmol/L (95% credible interval: 24.6, 26.4). The median pf-ITs were similar between the baseline and postsupplementation samples (25.7 compared with 25.2 nmol/L) but differed moderately (±3-4 nmol/L) by MTHFR genotype and BMI. Using the full population-based baseline sample (intervention and nonintervention), the median pf-IT was higher for women with vitamin B-12 deficiency (34.6 nmol/L) and marginal deficiency (29.8 nmol/L) compared with the sufficient group (25.6 nmol/L). CONCLUSIONS The relation between RBC and plasma folate concentrations was modified by BMI and genotype and substantially by low plasma vitamin B-12. This suggests that the threshold of 25.5 nmol/L for optimal NTD prevention may be appropriate in populations with similar characteristics, but it should not be used in vitamin B-12 insufficient populations. This trial was registered at clinicaltrials.gov as NCT00207558.
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MPP1-based mechanism of resting state raft organization in the plasma membrane. Is it a general or specialized mechanism in erythroid cells?
Trybus, M, Niemiec, L, Biernatowska, A, Hryniewicz-Jankowska, A, Sikorski, AF
Folia histochemica et cytobiologica. 2019;(2):43-55
Abstract
Biological membranes are organized in various microdomains, one of the best known being called membrane rafts. The major function of these is thought to organize signaling partners into functional complexes. An important protein found in membrane raft microdomains of erythroid and other blood cells is MPP1 (membrane palmitoylated protein 1)/p55. MPP1 (p55) belongs to the MAGUK (membrane-associated guanylate kinase homolog) family and it is a major target of palmitoylation in the red blood cells (RBCs) membrane. The well-known function of this protein is to participate in formation of the junctional complex of the erythrocyte mem-brane skeleton. However, its function as a "raft organizer" is not well understood. In this review we focus on recent reports concerning MPP1 participation in membrane rafts organization in erythroid cells, including its role in signal transduction. Currently it is not known whether MPP1 could have a similar role in cell types other than erythroid lineage. We present also preliminary data regarding the expression level of MPP1 gene in several non-erythroid cell lines.
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Evaluation of plasma and erythrocyte fatty acids C15:0, t-C16:1n-7 and C17:0 as biomarkers of dairy fat consumption in adolescents.
Slim, M, Ha, C, Vanstone, CA, Morin, SN, Rahme, E, Weiler, HA
Prostaglandins, leukotrienes, and essential fatty acids. 2019;:24-29
Abstract
INTRODUCTION Pentadecanoic (C15:0), heptadecanoic (C17:0) and trans-palmitoleic (t-C16:1n-7) fatty acids (FAs) are often used as biomarkers for dairy fat in adults. This study aimed to investigate the relationship between dairy product intake and these FAs in adolescents. MATERIAL AND METHODS Healthy adolescents were randomized to one of three groups (Group 1: control; Group 2: consume 3 dairy servings/day; and Group 3: consume ≥ 4 servings/d). C15:0, C17:0 and t-C16:1n-7 were quantified using gas chromatography. Dietary intakes were assessed by 24 h diet recalls. RESULTS No difference was observed in FAs at baseline or 6 months (mo), however, at 12 mo, erythrocyte C15:0 increased in group 3 (+0.37 µg/ml, p = 0.01). Dairy intake increased in both intervention groups (Group 2: +1.4 servings/d; Group 3: +2.4 servings/d, p < 0.0001) and positively correlated with erythrocyte C15:0 at 12 mo. CONCLUSION Erythrocyte FAs appear to be associated with increasing dairy intakes during adolescence.
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The long and winding road to pathogen reduction of platelets, red blood cells and whole blood.
Rebulla, P
British journal of haematology. 2019;(5):655-667
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Abstract
Pathogen reduction technologies (PRTs) have been developed to further reduce the current very low risks of acquiring transfusion-transmitted infections and promptly respond to emerging infectious threats. An entire portfolio of PRTs suitable for all blood components is not available, but the field is steadily progressing. While PRTs for plasma have been used for many years, PRTs for platelets, red blood cells (RBC) and whole blood (WB) were developed more slowly, due to difficulties in preserving cell functions during storage. Two commercial platelet PRTs use ultra violet (UV) A and UVB light in the presence of amotosalen or riboflavin to inactivate pathogens' nucleic acids, while a third experimental PRT uses UVC light only. Two PRTs for WB and RBC have been tested in experimental clinical trials with storage limited to 21 or 35 days, due to unacceptably high RBC storage lesion beyond these time limits. This review summarizes pre-clinical investigations and selected outcomes from clinical trials using the above PRTs. Further studies are warranted to decrease cell storage lesions after PRT treatment and to test PRTs in different medical and surgical conditions. Affordability remains a major administrative obstacle to PRT use, particularly so in geographical regions with higher risks of transfusion-transmissible infections.
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Evaluation of riboflavin photochemical treatment for inactivation of HCT116 tumor cells mixed in simulative intraoperative salvage blood.
Yu, Y, Yang, L, He, C, Tai, S, Ma, C, Yang, T, Wang, D
Transfusion. 2019;(10):3205-3213
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Abstract
BACKGROUND Radiation and filtration have achieved satisfactory results in inactivation or removal of tumor cells mixed in salvage blood, but some drawbacks remain. This study evaluated the inactivation on HCT116 cells mixed in simulative salvage blood by riboflavin photochemical treatment. METHODS HCT116 cells were added to the whole blood to simulate contaminated salvaged blood. The mixed blood was added with riboflavin of 50 μmol/L final concentration and illuminated by ultraviolet light. The samples were divided into control group and Experimental Groups 1 (18 J/cm2 ), 2 (23.4 J/cm2 ), and 3 (28.8 J/cm2 ). An autotransfusion system (Cell Saver Elite, Haemonetics) was used to simulate the intraoperative blood salvage procedure to deal with whole blood. The apoptosis rate and tumorigenicity of HCT116 cells and the superimposed damage to red blood cells (RBCs) were evaluated. RESULTS The apoptosis rates of HCT116 in Experimental Groups 1, 2, and 3 were much higher than that in the control group. Tumor growth was found in the control group, but no tumor growth was found in the three experimental groups. The hemolysis rates in the three experimental groups were significantly higher than that in the control group, but much lower than the quality standard of RBCs at the end of preservation. The concentration of adenosine triphosphate in RBCs was comparable in the control and experimental groups. CONCLUSION Riboflavin at a 50 μmol/L final concentration and 18 J/cm2 ultraviolet illumination can effectively inactivate HCT116 cells in salvaged blood, with minimum damage to the structure and function of RBCs, and the main quality indexes of salvaged RBCs were within the standard range.
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Protective Effect of Dinitrosyl Iron Complexes with Glutathione in Red Blood Cell Lysis Induced by Hypochlorous Acid.
Shumaev, KB, Gorudko, IV, Kosmachevskaya, OV, Grigorieva, DV, Panasenko, ОM, Vanin, AF, Topunov, AF, Terekhova, MS, Sokolov, AV, Cherenkevich, SN, et al
Oxidative medicine and cellular longevity. 2019;:2798154
Abstract
Hypochlorous acid (HOCl), one of the major precursors of free radicals in body cells and tissues, is endowed with strong prooxidant activity. In living systems, dinitrosyl iron complexes (DNIC) with glutathione ligands play the role of nitric oxide donors and possess a broad range of biological activities. At micromolar concentrations, DNIC effectively inhibit HOCl-induced lysis of red blood cells (RBCs) and manifest an ability to scavenge alkoxyl and alkylperoxyl radicals generated in the reaction of HOCl with tert-butyl hydroperoxide. DNIC proved to be more effective cytoprotective agents and organic free radical scavengers in comparison with reduced glutathione (GSH). At the same time, the kinetics of HOCl-induced oxidation of glutathione ligands in DNIC is slower than in the case of GSH. HOCl-induced oxidative conversions of thiolate ligands cause modification of DNIC, which manifests itself in inclusion of other ligands. It is suggested that the strong inhibiting effect of DNIC with glutathione on HOCl-induced lysis of RBCs is determined by their antioxidant and regulatory properties.
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Relationship between erythrocyte phospholipid fatty acid composition and obesity in children and adolescents.
Tang, J, Yan, Y, Li, J, Yang, B, Zhao, X, Wan, Y, Zheng, JS, Mi, J, Li, D
Journal of clinical lipidology. 2019;(1):70-79.e1
Abstract
BACKGROUND Observational studies have reported inconsistent results on the association between circulating fatty acids and obesity. OBJECTIVE The objective of this study was to investigate the relationship between erythrocyte phospholipid fatty acid composition and obesity in children and adolescents. METHODS We conducted a case-control study including 1442 obese and 1442 normal-weight children and adolescents. Circulating fatty acid composition between cases and controls were compared both in the present study and literature-based meta-analysis. Individual fatty acids contributing most to discriminating cases and controls were identified by orthogonal partial least squares-discriminant analysis and their associations with obesity were explored by a conditional logistic regression model. RESULTS Five saturated fatty acids (14:0, 16:0, 17:0, 18:0, 20:0) were higher, 9 polyunsaturated fatty acids (18:3n-3, 20:3n-3, 20:5n-3, 22:5n-3, 22:6n-3, 18:2n-6, 20:2n-6, 20:3n-6, 20:4n-6) were lower in cases than in controls, while pooled results from the comparative meta-analysis were only consistent in 22:5n-3, 22:6n-3 and 18:2n-6. The orthogonal partial least squares-discriminant analysis model indicated that 16:0, 18:0, 20:4n-6, and 22:6n-3 were the fatty acids contributing most to discriminating cases and controls. In the conditional logistic regression model, significant positive associations were found for 16:0 (per 1 SD OR = 1.43, 95% CI, 1.35-1.52) and 18:0 (per 1 SD OR = 1.12, 95% CI, 1.09-1.16), while significant inverse associations were found for 20:4n-6 (per 1 SD OR = 0.63, 95% CI, 0.58-0.69) and 22:6n-3 (per 1 SD OR = 0.56, 95% CI, 0.52-0.61). CONCLUSIONS Erythrocyte phospholipid 16:0 and 18:0 were positively and 20:4n-6 and 22:6n-3 were inversely associated with obesity in children and adolescents.
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The red blood cell proportion of arachidonic acid relates to shorter leukocyte telomeres in Mediterranean elders: A secondary analysis of a randomized controlled trial.
Freitas-Simoes, TM, Cofán, M, Blasco, MA, Soberón, N, Foronda, M, Corella, D, Asensio, EM, Serra-Mir, M, Roth, I, Calvo, C, et al
Clinical nutrition (Edinburgh, Scotland). 2019;(2):958-961
Abstract
BACKGROUND & AIMS Shortening of leukocyte telomere length (LTL) is a biomarker of aging. Epidemiologic studies of LTL in relation to dietary fatty acids have reported conflicting results. The red blood cell (RBC) fatty acid status is a valid objective biomarker of long-term dietary intake of C18:2n-6, C18:3n-3 and long-chain n-3 polyunsaturated fatty acids (C20:5n-3 and C22:6n-3). In healthy older individuals, we investigated whether LTL relates to the RBC proportions of the main dietary polyunsaturated fatty acids (PUFA), and to the RBC proportion of arachidonic acid (C20:4n-6), a fatty acid that can generate pro-inflammatory lipid mediators once released from cell membranes. DESIGN Cross-sectional study in 344 subjects (mean age 68.8 y, 68.6% women) who participated in a randomized controlled trial testing whether a diet enriched in walnuts can delay the onset of age-related diseases (https://clinicaltrials.gov/ct2/show/NCT01634841). At baseline, we assessed LTL by high-throughput quantitative fluorescence and determined fatty acids in RBCs by gas chromatography. RESULTS In multivariate models adjusted for age and gender, the RBC proportions of dietary PUFA were unrelated to LTL. In contrast, the RBC proportion of arachidonic acid inversely related to LTL (regression coefficient [95% confidence interval], -0.10 (-0.19 to -0.01), P = 0.023). CONCLUSION An increasing proportion of C20:4n-6 in RBCs is associated with shorter telomeres. Further research is needed to investigate the role of this fatty acid and its derived lipid mediators in the aging process.