{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T12:51:03Z","timestamp":1784119863921,"version":"3.55.0"},"reference-count":60,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T00:00:00Z","timestamp":1679616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Vetsuisse Faculty, University of Bern","award":["CRSII5_180234"],"award-info":[{"award-number":["CRSII5_180234"]}]},{"DOI":"10.13039\/501100001711","name":"SNSF","doi-asserted-by":"publisher","award":["CRSII5_180234"],"award-info":[{"award-number":["CRSII5_180234"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Methemoglobinemia is an acquired or inherited condition resulting from oxidative stress or dysfunction of the NADH-cytochrome b5 reductase or associated pathways. This study describes the clinical, pathophysiological, and molecular genetic features of a cat with hereditary methemoglobinemia. Whole genome sequencing and mRNA transcript analyses were performed in affected and control cats. Co-oximetry, ektacytometry, Ellman\u2019s assay for reduced glutathione concentrations, and CYB5R activity were assessed. A young adult European domestic shorthair cat decompensated at induction of anesthesia and was found to have persistent methemoglobinemia of 39 \u00b1 8% (reference range &lt; 3%) of total hemoglobin which could be reversed upon intravenous methylene blue injection. The erythrocytic CYB5R activity was 20 \u00b1 6% of normal. Genetic analyses revealed a single homozygous base exchange at the beginning of intron 3 of the CYB5R3 gene, c.226+5G&gt;A. Subsequent mRNA studies confirmed a splice defect and demonstrated expression of two mutant CYB5R3 transcripts. Erythrocytic glutathione levels were twice that of controls. Mild microcytosis, echinocytes, and multiple Ca2+-filled vesicles were found in the affected cat. Erythrocytes were unstable at high osmolarities although highly deformable as follows from the changes in elongation index and maximal-tolerated osmolarity. Clinicopathological presentation of this cat was similar to other cats with CYB5R3 deficiency. We found that methemoglobinemia is associated with an increase in red blood cell fragility and deformability, glutathione overload, and morphological alterations typical for stress erythropoiesis.<\/jats:p>","DOI":"10.3390\/cells12070991","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T04:31:05Z","timestamp":1679632265000},"page":"991","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Methemoglobinemia, Increased Deformability and Reduced Membrane Stability of Red Blood Cells in a Cat with a CYB5R3 Splice Defect"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9577-5457","authenticated-orcid":false,"given":"Sophia","family":"Jenni","sequence":"first","affiliation":[{"name":"Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0691-1211","authenticated-orcid":false,"given":"Odette","family":"Ludwig-Peisker","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidhya","family":"Jagannathan","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Lapsina","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Department of Clinical Diagnostics and Services, and Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Stirn","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Department of Clinical Diagnostics and Services, and Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9750-4296","authenticated-orcid":false,"given":"Regina","family":"Hofmann-Lehmann","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Department of Clinical Diagnostics and Services, and Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolay","family":"Bogdanov","sequence":"additional","affiliation":[{"name":"Red Blood Cell Group, Institute of Veterinary Physiology and the Center for Clinical Studies, Vetsuisse Faculty Zurich, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelli","family":"Schetle","sequence":"additional","affiliation":[{"name":"Red Blood Cell Group, Institute of Veterinary Physiology and the Center for Clinical Studies, Vetsuisse Faculty Zurich, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4770-4107","authenticated-orcid":false,"given":"Urs","family":"Giger","sequence":"additional","affiliation":[{"name":"Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0553-4880","authenticated-orcid":false,"given":"Tosso","family":"Leeb","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0502-5381","authenticated-orcid":false,"given":"Anna","family":"Bogdanova","sequence":"additional","affiliation":[{"name":"Red Blood Cell Group, Institute of Veterinary Physiology and the Center for Clinical Studies, Vetsuisse Faculty Zurich, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102654","DOI":"10.1016\/j.jbc.2022.102654","article-title":"Cytochrome b5 reductases: Redox regulators of cell homeostasis","volume":"298","author":"Hall","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/BF03259842","article-title":"Drug- and chemical-induced methaemoglobinaemia. Clinical features and management","volume":"1","author":"Hall","year":"1986","journal-title":"Med. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/ajh.2830420104","article-title":"Concise review: Methemoglobinemia","volume":"42","author":"Mansouri","year":"1993","journal-title":"Am. J. Hematol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0308-2261(21)00211-3","article-title":"Methaemoglobinaemia","volume":"10","author":"Jaffe","year":"1981","journal-title":"Clin. Haematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/j.1365-2141.2008.07017.x","article-title":"Recessive congenital methaemoglobinaemia: Cytochrome b(5) reductase deficiency","volume":"141","author":"Percy","year":"2008","journal-title":"Br. J. Haematol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1354\/vp.40-6-632","article-title":"Methemoglobinemia and eccentrocytosis in equine erythrocyte flavin adenine dinucleotide deficiency","volume":"40","author":"Harvey","year":"2003","journal-title":"Vet. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1002\/humu.23973","article-title":"Mutation update: Variants of the CYB5R3 gene in recessive congenital methemoglobinemia","volume":"41","author":"Gupta","year":"2020","journal-title":"Hum. Mutat."},{"key":"ref_8","first-page":"81","article-title":"Enzymopenic hereditary methemoglobinemia: A clinical\/biochemical classification","volume":"12","author":"Jaffe","year":"1986","journal-title":"Blood Cells"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/S0196-0644(99)70167-8","article-title":"Methemoglobinemia: Etiology, pharmacology, and clinical management","volume":"34","author":"Wright","year":"1999","journal-title":"Ann. Emerg. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1093\/brain\/awm337","article-title":"Recessive hereditary methaemoglobinaemia, type II: Delineation of the clinical spectrum","volume":"131","author":"Ewenczyk","year":"2008","journal-title":"Brain"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Siendones, E., Ballesteros, M., and Navas, P. (2018). Cellular and Molecular Mechanisms of Recessive Hereditary Methaemoglobinaemia Type II. J. Clin. Med., 7.","DOI":"10.3390\/jcm7100341"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1007\/s11033-021-07031-3","article-title":"Three novel mutations in CYB5R3 gene causing NADH-cytochrome b5 reductase enzyme deficiency leads to recessive congenital methaemoglobinemia","volume":"49","author":"Deorukhkar","year":"2022","journal-title":"Mol. Biol. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ullah, A., Shah, A.A., Syed, F., Mahmood, A., Ur Rehman, H., Khurshid, B., Samad, A., Ahmad, W., and Basit, S. (2023). Molecular Dynamic Simulation Analysis of a Novel Missense Variant in CYB5R3 Gene in Patients with Methemoglobinemia. Medicina, 59.","DOI":"10.3390\/medicina59020379"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/j.1939-165X.2006.tb00108.x","article-title":"Pathogenesis, laboratory diagnosis, and clinical implications of erythrocyte enzyme deficiencies in dogs, cats, and horses","volume":"35","author":"Harvey","year":"2006","journal-title":"Vet. Clin. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/0305-0491(75)90226-6","article-title":"Erythrocyte enzyme activities and glutathione levels of the horse, cat, dog and man","volume":"52","author":"Harvey","year":"1975","journal-title":"Comp. Biochem. Physiol. B"},{"key":"ref_16","first-page":"1030","article-title":"Methemoglobin reductase deficiency in a dog","volume":"164","author":"Harvey","year":"1974","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1111\/jvim.14843","article-title":"Long-term Treatment with Methylene Blue in a Dog with Hereditary Methemoglobinemia Caused by Cytochrome b5 Reductase Deficiency","volume":"31","author":"Jaffey","year":"2017","journal-title":"J. Vet. Intern. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21399","DOI":"10.1038\/s41598-020-78391-2","article-title":"Clinical, metabolic, and molecular genetic characterization of hereditary methemoglobinemia caused by cytochrome b5 reductase deficiency in 30 dogs","volume":"10","author":"Jaffey","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1111\/jvim.12423","article-title":"Congenital methemoglobinemia in a dog with a promoter deletion and a nonsynonymous coding variant in the gene encoding cytochrome b(5)","volume":"28","author":"McKenna","year":"2014","journal-title":"J. Vet. Intern. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/jvim.15031","article-title":"Familial Congenital Methemoglobinemia in Pomeranian Dogs Caused by a Missense Variant in the NADH-Cytochrome B5 Reductase Gene","volume":"32","author":"Shino","year":"2018","journal-title":"J. Vet. Intern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1111\/jvim.15435","article-title":"Genetic cause for congenital methemoglobinemia in an Australian Pomeranian dog","volume":"33","author":"Zhou","year":"2019","journal-title":"J. Vet. Intern. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.2460\/javma.1994.205.09.1290","article-title":"Methemoglobin reductase deficiency in a cat","volume":"205","author":"Harvey","year":"1994","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1111\/jvim.15637","article-title":"Clinical, metabolic, and genetic characterization of hereditary methemoglobinemia caused by cytochrome b5 reductase deficiency in cats","volume":"33","author":"Jaffey","year":"2019","journal-title":"J. Vet. Intern. Med."},{"key":"ref_24","first-page":"120","article-title":"Methylene blue can be used to treat methemoglobinemia in cats without inducing Heinz body hemolytic anemia","volume":"34","author":"Rumbeiha","year":"1992","journal-title":"Vet. Hum. Toxicol."},{"key":"ref_25","first-page":"502","article-title":"Hereditary methemoglobinemia in a cyanotic cat presented for ovariohysterectomy","volume":"60","author":"Vasiliadou","year":"2019","journal-title":"Can. Vet. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/S0195-5616(96)50052-5","article-title":"Congenital erythrocyte enzyme deficiencies","volume":"26","author":"Harvey","year":"1996","journal-title":"Vet. Clin. N. Am. Small Anim. Pract."},{"key":"ref_27","first-page":"339","article-title":"New method for determining ferrihemoglobin reductase (NADH-methemoglobin reductase) in erythrocytes","volume":"72","author":"Hegesh","year":"1968","journal-title":"J. Lab. Clin. Med."},{"key":"ref_28","unstructured":"Beutler, E. (1975). Red Cell Metabolism. A Manual of Biochemical Methods, Grune & Stratton."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/0003-2697(69)90064-5","article-title":"Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: Applications to mammalian blood and other tissues","volume":"27","author":"Tietze","year":"1969","journal-title":"Anal. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s00232-003-2042-8","article-title":"Pivotal role of reduced glutathione in oxygen-induced regulation of the Na(+)\/K(+) pump in mouse erythrocyte membranes","volume":"195","author":"Bogdanova","year":"2003","journal-title":"J. Membr. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"639722","DOI":"10.3389\/fphys.2021.639722","article-title":"Donor Age and Red Cell Age Contribute to the Variance in Lorrca Indices in Healthy Donors for Next Generation Ektacytometry: A Pilot Study","volume":"12","author":"Fenk","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/age.12834","article-title":"A comprehensive biomedical variant catalogue based on whole genome sequences of 582 dogs and eight wolves","volume":"50","author":"Jagannathan","year":"2019","journal-title":"Anim. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3","volume":"6","author":"Cingolani","year":"2012","journal-title":"Fly"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41592-022-01488-1","article-title":"ColabFold: Making protein folding accessible to all","volume":"19","author":"Mirdita","year":"2022","journal-title":"Nat. Methods"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Burkitt Creedon, J.M., and Davis, H. (2012). Advanced Monitoring and Procedured for Small Animal Emergency and Critical Care, Willey-Blackwell.","DOI":"10.1002\/9781118997246"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"656","DOI":"10.3389\/fphys.2018.00656","article-title":"Squeezing for Life\u2014Properties of Red Blood Cell Deformability","volume":"9","author":"Huisjes","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.tcb.2008.04.005","article-title":"The meaning of nonsense","volume":"18","author":"Stalder","year":"2008","journal-title":"Trends Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1292\/jvms.20-0390","article-title":"Characterization of a novel nicotinamide adenine dinucleotide-cytochrome b5 reductase mutation associated with canine hereditary methemoglobinemia","volume":"83","author":"Inanami","year":"2021","journal-title":"J. Vet. Med. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1373\/clinchem.2004.035154","article-title":"Laboratory assessment of oxygenation in methemoglobinemia","volume":"51","author":"Haymond","year":"2005","journal-title":"Clin. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5760","DOI":"10.1021\/bi400405p","article-title":"Membrane peroxidation and methemoglobin formation are both necessary for band 3 clustering: Mechanistic insights into human erythrocyte senescence","volume":"52","author":"Arashiki","year":"2013","journal-title":"Biochemistry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"R916","DOI":"10.1152\/ajpregu.00038.2005","article-title":"Na-K-ATPase in rat cerebellar granule cells is redox sensitive","volume":"290","author":"Petrushanko","year":"2006","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.bcmd.2006.09.003","article-title":"Membrane skeletal protein S-glutathionylation and hemolysis in human red blood cells","volume":"37","author":"Rossi","year":"2006","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1248\/bpb.33.1925","article-title":"Disruption of glutathione homeostasis causes accumulation of S-glutathionyl proteins in response to exposure to reactive oxygen species in human erythrocytes","volume":"33","author":"Ogasawara","year":"2010","journal-title":"Biol. Pharm. Bull."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1021\/acs.chemrestox.8b00408","article-title":"Membrane Skeletal Protein S-Glutathionylation in Human Red Blood Cells as Index of Oxidative Stress","volume":"32","author":"Giustarini","year":"2019","journal-title":"Chem. Res. Toxicol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jchromb.2016.01.032","article-title":"Evidence by chromatography and mass spectrometry that inorganic nitrite induces S-glutathionylation of hemoglobin in human red blood cells","volume":"1019","author":"Bohmer","year":"2016","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/bjh.13028","article-title":"Red blood cells of sickle cell disease patients exhibit abnormally high abundance of N-methyl D-aspartate receptors mediating excessive calcium uptake","volume":"167","author":"Hanggi","year":"2014","journal-title":"Br. J. Haematol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"673","DOI":"10.3389\/fphys.2017.00673","article-title":"Is Increased Intracellular Calcium in Red Blood Cells a Common Component in the Molecular Mechanism Causing Anemia?","volume":"8","author":"Hertz","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/jha2.11","article-title":"A pilot clinical phase II trial MemSID: Acute and durable changes of red blood cells of sickle cell disease patients on memantine treatment","volume":"1","author":"Makhro","year":"2020","journal-title":"eJHaem"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"893","DOI":"10.3389\/fphys.2019.00893","article-title":"Aging Markers in Equine Red Blood Cells","volume":"10","author":"Kampf","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"C1123","DOI":"10.1152\/ajpcell.00031.2013","article-title":"N-methyl-D-aspartate receptors in human erythroid precursor cells and in circulating red blood cells contribute to the intracellular calcium regulation","volume":"305","author":"Makhro","year":"2013","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1126\/science.120.3116.459","article-title":"Potassium and sodium balance in mammalian red cells","volume":"120","author":"Bernstein","year":"1954","journal-title":"Science"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1021\/bi201623v","article-title":"Interaction of deoxyhemoglobin with the cytoplasmic domain of murine erythrocyte band 3","volume":"51","author":"Sega","year":"2012","journal-title":"Biochemistry"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1182\/blood-2016-01-692079","article-title":"Reversible binding of hemoglobin to band 3 constitutes the molecular switch that mediates O2 regulation of erythrocyte properties","volume":"128","author":"Chu","year":"2016","journal-title":"Blood"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1182\/blood-2007-07-100180","article-title":"Characterization of the deoxyhemoglobin binding site on human erythrocyte band 3: Implications for O2 regulation of erythrocyte properties","volume":"111","author":"Chu","year":"2008","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1021\/bi00322a006","article-title":"Hemichrome binding to band 3: Nucleation of Heinz bodies on the erythrocyte membrane","volume":"24","author":"Waugh","year":"1985","journal-title":"Biochemistry"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/ijlh.12657","article-title":"Red cell membrane disorders","volume":"39","author":"Narla","year":"2017","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1042\/BJ20120869","article-title":"Oxygen regulates the band 3-ankyrin bridge in the human erythrocyte membrane","volume":"449","author":"Stefanovic","year":"2013","journal-title":"Biochem. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"eaaw4466","DOI":"10.1126\/sciadv.aaw4466","article-title":"Oxygen tension-mediated erythrocyte membrane interactions regulate cerebral capillary hyperemia","volume":"5","author":"Zhou","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"365","DOI":"10.3389\/fphys.2013.00365","article-title":"Red blood cell vesiculation in hereditary hemolytic anemia","volume":"4","author":"Alaarg","year":"2013","journal-title":"Front. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/202607a0","article-title":"A Comparision of the Effect of Menadione, Methylene Blue and Ascorbic Acid on the Reduction of Methemoglobin in Vivo","volume":"202","author":"Jaffe","year":"1964","journal-title":"Nature"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/7\/991\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:02:01Z","timestamp":1760122921000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/7\/991"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,24]]},"references-count":60,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["cells12070991"],"URL":"https:\/\/doi.org\/10.3390\/cells12070991","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,24]]}}}