Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept

Abstract: For some molecular players in red blood cells (RBCs), the functional indications and molecular evidence are discrepant. One such protein is transient receptor potential channel of canonical subfamily, member 6 (TRPC6). Transcriptome analysis of reticulocytes revealed the presence of TRPC6...

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Autores principales: Hertz, Laura, Flormann, Daniel, Birnbaumer, Lutz, Wagner, Christian, Laschke, Matthias W., Kaestner, Lars
Formato: Artículo
Lenguaje:Inglés
Publicado: American Society of Hematology 2023
Materias:
GLOBULOS ROJOS
HIERRO
ERITROPOYESIS
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/17371
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Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139-123456789-17371
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spelling I33-R139-123456789-173712023-11-23T18:11:13Z Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept Hertz, Laura Flormann, Daniel Birnbaumer, Lutz Wagner, Christian Laschke, Matthias W. Kaestner, Lars GLOBULOS ROJOS HIERRO ERITROPOYESIS Abstract: For some molecular players in red blood cells (RBCs), the functional indications and molecular evidence are discrepant. One such protein is transient receptor potential channel of canonical subfamily, member 6 (TRPC6). Transcriptome analysis of reticulocytes revealed the presence of TRPC6 in mouse RBCs and its absence in human RBCs. We transfused TRPC6 knockout RBCs into wild-type mice and performed functional tests. We observed the “rescue” of TRPC6 within 10 days; however, the “rescue” was slower in splenectomized mice. The latter finding led us to mimic the mechanical challenge with the cantilever of an atomic force microscope and simultaneously carry out imaging by confocal (3D) microscopy. We observed the strong interaction of RBCs with the opposed surface at around 200 pN and the formation of tethers. The results of both the transfusion experiments and the atomic force spectroscopy suggest mechanically stimulated protein transfer to RBCs as a protein source in the absence of the translational machinery. This protein transfer mechanism has the potential to be utilized in therapeutic contexts, especially for hereditary diseases involving RBCs, such as hereditary xerocytosis or Gárdos channelopathy. 2023-10-31T10:38:08Z 2023-10-31T10:38:08Z 2023 Artículo Hertz, L. et al. Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept [en línea]. Blood Advances. 2023, 7(6). doi: 10.1182/bloodadvances.2022008404. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/17371 2473-9537 (online) https://repositorio.uca.edu.ar/handle/123456789/17371 10.1182/bloodadvances.2022008404 36490356 eng Acceso abierto http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Society of Hematology Blood Advances. Vol.7, No.6, 2023
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic GLOBULOS ROJOS
HIERRO
ERITROPOYESIS
spellingShingle GLOBULOS ROJOS
HIERRO
ERITROPOYESIS
Hertz, Laura
Flormann, Daniel
Birnbaumer, Lutz
Wagner, Christian
Laschke, Matthias W.
Kaestner, Lars
Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept
topic_facet GLOBULOS ROJOS
HIERRO
ERITROPOYESIS
description Abstract: For some molecular players in red blood cells (RBCs), the functional indications and molecular evidence are discrepant. One such protein is transient receptor potential channel of canonical subfamily, member 6 (TRPC6). Transcriptome analysis of reticulocytes revealed the presence of TRPC6 in mouse RBCs and its absence in human RBCs. We transfused TRPC6 knockout RBCs into wild-type mice and performed functional tests. We observed the “rescue” of TRPC6 within 10 days; however, the “rescue” was slower in splenectomized mice. The latter finding led us to mimic the mechanical challenge with the cantilever of an atomic force microscope and simultaneously carry out imaging by confocal (3D) microscopy. We observed the strong interaction of RBCs with the opposed surface at around 200 pN and the formation of tethers. The results of both the transfusion experiments and the atomic force spectroscopy suggest mechanically stimulated protein transfer to RBCs as a protein source in the absence of the translational machinery. This protein transfer mechanism has the potential to be utilized in therapeutic contexts, especially for hereditary diseases involving RBCs, such as hereditary xerocytosis or Gárdos channelopathy.
format Artículo
author Hertz, Laura
Flormann, Daniel
Birnbaumer, Lutz
Wagner, Christian
Laschke, Matthias W.
Kaestner, Lars
author_facet Hertz, Laura
Flormann, Daniel
Birnbaumer, Lutz
Wagner, Christian
Laschke, Matthias W.
Kaestner, Lars
author_sort Hertz, Laura
title Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept
title_short Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept
title_full Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept
title_fullStr Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept
title_full_unstemmed Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept
title_sort evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept
publisher American Society of Hematology
publishDate 2023
url https://repositorio.uca.edu.ar/handle/123456789/17371
work_keys_str_mv AT hertzlaura evidenceofinvivoexogenproteinuptakebyredbloodcellsaputativetherapeuticconcept
AT flormanndaniel evidenceofinvivoexogenproteinuptakebyredbloodcellsaputativetherapeuticconcept
AT birnbaumerlutz evidenceofinvivoexogenproteinuptakebyredbloodcellsaputativetherapeuticconcept
AT wagnerchristian evidenceofinvivoexogenproteinuptakebyredbloodcellsaputativetherapeuticconcept
AT laschkematthiasw evidenceofinvivoexogenproteinuptakebyredbloodcellsaputativetherapeuticconcept
AT kaestnerlars evidenceofinvivoexogenproteinuptakebyredbloodcellsaputativetherapeuticconcept
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