Dysregulated Erythroid Mg2+ Efflux in Type 2 Diabetes

Detalhes bibliográficos
Autor(a) principal: Ferreira, Ana
Data de Publicação: 2022
Outros Autores: Rivera, Alicia, Wohlgemuth, Jay G., Dlott, Jeffrey S., Snyder, L. Michael, Alper, Seth L., Romero, Jose R.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/144598
Resumo: CEECIND/01053/2017 UIDB/04647/2020 UIDP/04647/2020
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spelling Dysregulated Erythroid Mg2+ Efflux in Type 2 DiabetesCell magnesiumDiabetes mellitusIIon exchangeIon fluxIon transporterRed blood cellsDevelopmental BiologyCell BiologySDG 3 - Good Health and Well-beingCEECIND/01053/2017 UIDB/04647/2020 UIDP/04647/2020Hyperglycemia is associated with decreased Mg2+ content in red blood cells (RBC), but mechanisms remain unclear. We characterized the regulation of Mg2+ efflux by glucose in ex vivo human RBC. We observed that hemoglobin A1C (HbA1C) values correlated with Na+-dependent Mg2+ efflux (Na+/Mg2+ exchange) and inversely correlated with cellular Mg content. Treatment of cells with 50 mM D-glucose, but not with sorbitol, lowered total cellular Mg (2.2 ± 0.1 to 2.0 ± 0.1 mM, p < 0.01) and enhanced Na+/Mg2+ exchange activity [0.60 ± 0.09 to 1.12 ± 0.09 mmol/1013 cell × h (flux units, FU), p < 0.05]. In contrast, incubation with selective Src family kinase inhibitors PP2 or SU6656 reduced glucose-stimulated exchange activation (p < 0.01). Na+/Mg2+ exchange activity was also higher in RBC from individuals with type 2 diabetes (T2D, 1.19 ± 0.13 FU) than from non-diabetic individuals (0.58 ± 0.05 FU, p < 0.01). Increased Na+/Mg2+ exchange activity in RBC from T2D subjects was associated with lower intracellular Mg content. Similarly increased exchange activity was evident in RBC from the diabetic db/db mouse model as compared to its non-diabetic control (p < 0.03). Extracellular exposure of intact RBC from T2D subjects to recombinant peptidyl-N-glycosidase F (PNGase F) reduced Na+/Mg2+ exchange activity from 0.98 ± 0.14 to 0.59 ± 0.13 FU (p < 0.05) and increased baseline intracellular Mg content (1.8 ± 0.1 mM) to normal values (2.1 ± 0.1 mM, p < 0.05). These data suggest that the reduced RBC Mg content of T2D RBC reflects enhanced RBC Na+/Mg2+ exchange subject to regulation by Src family kinases and by the N-glycosylation state of one or more membrane proteins. The data extend our understanding of dysregulated RBC Mg2+ homeostasis in T2D.Centro Interdisciplinar de Ciências Sociais (CICS.NOVA - NOVA FCSH)RUNFerreira, AnaRivera, AliciaWohlgemuth, Jay G.Dlott, Jeffrey S.Snyder, L. MichaelAlper, Seth L.Romero, Jose R.2022-10-11T22:24:34Z2022-04-042022-04-04T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article13application/pdfhttp://hdl.handle.net/10362/144598eng2296-634XPURE: 47028546https://doi.org/10.3389/fcell.2022.861644info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:24:17Zoai:run.unl.pt:10362/144598Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:51:38.279589Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Dysregulated Erythroid Mg2+ Efflux in Type 2 Diabetes
title Dysregulated Erythroid Mg2+ Efflux in Type 2 Diabetes
spellingShingle Dysregulated Erythroid Mg2+ Efflux in Type 2 Diabetes
Ferreira, Ana
Cell magnesium
Diabetes mellitus
IIon exchange
Ion flux
Ion transporter
Red blood cells
Developmental Biology
Cell Biology
SDG 3 - Good Health and Well-being
title_short Dysregulated Erythroid Mg2+ Efflux in Type 2 Diabetes
title_full Dysregulated Erythroid Mg2+ Efflux in Type 2 Diabetes
title_fullStr Dysregulated Erythroid Mg2+ Efflux in Type 2 Diabetes
title_full_unstemmed Dysregulated Erythroid Mg2+ Efflux in Type 2 Diabetes
title_sort Dysregulated Erythroid Mg2+ Efflux in Type 2 Diabetes
author Ferreira, Ana
author_facet Ferreira, Ana
Rivera, Alicia
Wohlgemuth, Jay G.
Dlott, Jeffrey S.
Snyder, L. Michael
Alper, Seth L.
Romero, Jose R.
author_role author
author2 Rivera, Alicia
Wohlgemuth, Jay G.
Dlott, Jeffrey S.
Snyder, L. Michael
Alper, Seth L.
Romero, Jose R.
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Centro Interdisciplinar de Ciências Sociais (CICS.NOVA - NOVA FCSH)
RUN
dc.contributor.author.fl_str_mv Ferreira, Ana
Rivera, Alicia
Wohlgemuth, Jay G.
Dlott, Jeffrey S.
Snyder, L. Michael
Alper, Seth L.
Romero, Jose R.
dc.subject.por.fl_str_mv Cell magnesium
Diabetes mellitus
IIon exchange
Ion flux
Ion transporter
Red blood cells
Developmental Biology
Cell Biology
SDG 3 - Good Health and Well-being
topic Cell magnesium
Diabetes mellitus
IIon exchange
Ion flux
Ion transporter
Red blood cells
Developmental Biology
Cell Biology
SDG 3 - Good Health and Well-being
description CEECIND/01053/2017 UIDB/04647/2020 UIDP/04647/2020
publishDate 2022
dc.date.none.fl_str_mv 2022-10-11T22:24:34Z
2022-04-04
2022-04-04T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/144598
url http://hdl.handle.net/10362/144598
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2296-634X
PURE: 47028546
https://doi.org/10.3389/fcell.2022.861644
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 13
application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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