TRPC proteins contribute to development of diabetic retinopathy and regulate glyoxalase 1 activity and methylglyoxal accumulation
- Autores
- Sachdeva, Robin; Schlotterer, Andrea; Schumacher, Dagmar; Matka, Christin; Mathar, Ilka; Dietrich, Nadine; Medert, Rebekka; Kriebs, Ulrich; Lin, Jihong; Nawroth, Peter; Birnbaumer, Lutz; Fleming, Thomas; Freichel, Marc; Hammes, Hans Peter
- Año de publicación
- 2018
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Fil: Sachdeva, Robin. Heidelberg Universit. Institute of Pharmacology; Alemania
Fil: Schlotterer, Andrea. Heidelberg Universit. Medical Faculty Mannheim. Vth Department of Medicine; Alemania
Fil: Schumacher, Dagmar. Heidelberg Universit. Institute of Pharmacology; Alemania
Fil: Matka, Christin. Heidelberg Universit. Institute of Pharmacology; Alemania
Fil: Mathar, Ilka. Heidelberg Universit. Institute of Pharmacology; Alemania
Fil: Dietrich, Nadine. Heidelberg Universit. Medical Faculty Mannheim. Vth Department of Medicine; Alemania
Fil: Medert, Rebekka. Heidelberg Universit. Institute of Pharmacology; Alemania
Fil: Kriebs, Ulrich. Heidelberg Universit. Institute of Pharmacology; Alemania
Fil: Lin, Jihong. Heidelberg Universit. Medical Faculty Mannheim. Vth Department of Medicine; Alemania
Fil: Nawroth, Peter. University Hospital Heidelberg. Department of Medicine I and Clinical Chemistry; Alemania
Fil: Nawroth, Peter. German Center for Diabetes Research; Alemania
Fil: Nawroth, Peter. Institute for Diabetes and Cancer IDC Helmholtz Center Munich; Alemania
Fil: Nawroth, Peter. eidelberg University Hospital. Departament of Medicine I. Joint Heidelberg Institute for Diabetes and Cancer Translational Diabetes Program; Alemania
Fil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences. Neurobiology Laboratoy; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Hammes, Hans-Peter. Heidelberg Universit. Medical Faculty Mannheim. Vth Department of Medicine; Alemania
Fil: Freichel, Marc. Heidelberg Universit. Institute of Pharmacology; Alemania
Objective Diabetic retinopathy (DR) is induced by an accumulation of reactive metabolites such as ROS, RNS, and RCS species, which were reported to modulate the activity of cation channels of the TRPC family. In this study, we use Trpc1/4/5/6−/− compound knockout mice to analyze the contribution of these TRPC proteins to diabetic retinopathy. Methods We used Nanostring- and qPCR-based analysis to determine mRNA levels of TRPC channels in control and diabetic retinae and retinal cell types. Chronic hyperglycemia was induced by Streptozotocin (STZ) treatment. To assess the development of diabetic retinopathy, vasoregression, pericyte loss, and thickness of individual retinal layers were analyzed. Plasma and cellular methylglyoxal (MG) levels, as well as Glyoxalase 1 (GLO1) enzyme activity and protein expression, were measured in WT and Trpc1/4/5/6−/− cells or tissues. MG-evoked toxicity in cells of both genotypes was compared by MTT assay. Results: We find that Trpc1/4/5/6−/− mice are protected from hyperglycemia-evoked vasoregression determined by the formation of acellular capillaries and pericyte drop-out. In addition, Trpc1/4/5/6−/− mice are resistant to the STZ-induced reduction in retinal layer thickness. The RCS metabolite methylglyoxal, which represents a key mediator for the development of diabetic retinopathy, was significantly reduced in plasma and red blood cells (RBCs) of STZ-treated Trpc1/4/5/6−/− mice compared to controls. GLO1 is the major MG detoxifying enzyme, and its activity and protein expression were significantly elevated in Trpc1/4/5/6-deficient cells, which led to significantly increased resistance to MG toxicity. GLO1 activity was also increased in retinal extracts from Trpc1/4/5/6−/− mice. The TRPCs investigated here are expressed at different levels in endothelial and glial cells of the retina. Conclusion The protective phenotype in diabetic retinopathy observed in Trpc1/4/5/6−/− mice is suggestive of a predominant action of TRPCs in Müller cells and microglia because of their central position in the retention of a proper homoeostasis of the neurovascular unit. - Fuente
- Molecular Metabolism. 2018;9:156-167
- Materia
-
RETINOPATIA DIABETICA
ENFERMEDADES METABOLICAS
HIPERGLUCEMIA - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/4.0/
- Repositorio
- Institución
- Pontificia Universidad Católica Argentina
- OAI Identificador
- oai:ucacris:123456789/8705
Ver los metadatos del registro completo
id |
RIUCA_04d76a0e13af5dd2971f3a0ae3ba479f |
---|---|
oai_identifier_str |
oai:ucacris:123456789/8705 |
network_acronym_str |
RIUCA |
repository_id_str |
2585 |
network_name_str |
Repositorio Institucional (UCA) |
spelling |
TRPC proteins contribute to development of diabetic retinopathy and regulate glyoxalase 1 activity and methylglyoxal accumulationSachdeva, RobinSchlotterer, AndreaSchumacher, DagmarMatka, ChristinMathar, IlkaDietrich, NadineMedert, RebekkaKriebs, UlrichLin, JihongNawroth, PeterBirnbaumer, LutzFleming, ThomasFreichel, MarcHammes, Hans PeterRETINOPATIA DIABETICAENFERMEDADES METABOLICASHIPERGLUCEMIAFil: Sachdeva, Robin. Heidelberg Universit. Institute of Pharmacology; AlemaniaFil: Schlotterer, Andrea. Heidelberg Universit. Medical Faculty Mannheim. Vth Department of Medicine; AlemaniaFil: Schumacher, Dagmar. Heidelberg Universit. Institute of Pharmacology; AlemaniaFil: Matka, Christin. Heidelberg Universit. Institute of Pharmacology; AlemaniaFil: Mathar, Ilka. Heidelberg Universit. Institute of Pharmacology; AlemaniaFil: Dietrich, Nadine. Heidelberg Universit. Medical Faculty Mannheim. Vth Department of Medicine; AlemaniaFil: Medert, Rebekka. Heidelberg Universit. Institute of Pharmacology; AlemaniaFil: Kriebs, Ulrich. Heidelberg Universit. Institute of Pharmacology; AlemaniaFil: Lin, Jihong. Heidelberg Universit. Medical Faculty Mannheim. Vth Department of Medicine; AlemaniaFil: Nawroth, Peter. University Hospital Heidelberg. Department of Medicine I and Clinical Chemistry; AlemaniaFil: Nawroth, Peter. German Center for Diabetes Research; AlemaniaFil: Nawroth, Peter. Institute for Diabetes and Cancer IDC Helmholtz Center Munich; AlemaniaFil: Nawroth, Peter. eidelberg University Hospital. Departament of Medicine I. Joint Heidelberg Institute for Diabetes and Cancer Translational Diabetes Program; AlemaniaFil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences. Neurobiology Laboratoy; Estados UnidosFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; ArgentinaFil: Hammes, Hans-Peter. Heidelberg Universit. Medical Faculty Mannheim. Vth Department of Medicine; AlemaniaFil: Freichel, Marc. Heidelberg Universit. Institute of Pharmacology; AlemaniaObjective Diabetic retinopathy (DR) is induced by an accumulation of reactive metabolites such as ROS, RNS, and RCS species, which were reported to modulate the activity of cation channels of the TRPC family. In this study, we use Trpc1/4/5/6−/− compound knockout mice to analyze the contribution of these TRPC proteins to diabetic retinopathy. Methods We used Nanostring- and qPCR-based analysis to determine mRNA levels of TRPC channels in control and diabetic retinae and retinal cell types. Chronic hyperglycemia was induced by Streptozotocin (STZ) treatment. To assess the development of diabetic retinopathy, vasoregression, pericyte loss, and thickness of individual retinal layers were analyzed. Plasma and cellular methylglyoxal (MG) levels, as well as Glyoxalase 1 (GLO1) enzyme activity and protein expression, were measured in WT and Trpc1/4/5/6−/− cells or tissues. MG-evoked toxicity in cells of both genotypes was compared by MTT assay. Results: We find that Trpc1/4/5/6−/− mice are protected from hyperglycemia-evoked vasoregression determined by the formation of acellular capillaries and pericyte drop-out. In addition, Trpc1/4/5/6−/− mice are resistant to the STZ-induced reduction in retinal layer thickness. The RCS metabolite methylglyoxal, which represents a key mediator for the development of diabetic retinopathy, was significantly reduced in plasma and red blood cells (RBCs) of STZ-treated Trpc1/4/5/6−/− mice compared to controls. GLO1 is the major MG detoxifying enzyme, and its activity and protein expression were significantly elevated in Trpc1/4/5/6-deficient cells, which led to significantly increased resistance to MG toxicity. GLO1 activity was also increased in retinal extracts from Trpc1/4/5/6−/− mice. The TRPCs investigated here are expressed at different levels in endothelial and glial cells of the retina. Conclusion The protective phenotype in diabetic retinopathy observed in Trpc1/4/5/6−/− mice is suggestive of a predominant action of TRPCs in Müller cells and microglia because of their central position in the retention of a proper homoeostasis of the neurovascular unit.Elsevier2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://repositorio.uca.edu.ar/handle/123456789/87052212-877810.1016/j.molmet.2018.01.00329373286Sachdeva R, Schlotterer A, Schumacher D, et al. TRPC proteins contribute to development of diabetic retinopathy and regulate glyoxalase 1 activity and methylglyoxal accumulation [en línea]. Molecular Metabolism. 2018;9:156-167. doi:10.1016/j.molmet.2018.01.003 Disponible en:Molecular Metabolism. 2018;9:156-167reponame:Repositorio Institucional (UCA)instname:Pontificia Universidad Católica Argentinaenginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/4.0/2025-07-03T10:56:54Zoai:ucacris:123456789/8705instacron:UCAInstitucionalhttps://repositorio.uca.edu.ar/Universidad privadaNo correspondehttps://repositorio.uca.edu.ar/oaiclaudia_fernandez@uca.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:25852025-07-03 10:56:55.055Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentinafalse |
dc.title.none.fl_str_mv |
TRPC proteins contribute to development of diabetic retinopathy and regulate glyoxalase 1 activity and methylglyoxal accumulation |
title |
TRPC proteins contribute to development of diabetic retinopathy and regulate glyoxalase 1 activity and methylglyoxal accumulation |
spellingShingle |
TRPC proteins contribute to development of diabetic retinopathy and regulate glyoxalase 1 activity and methylglyoxal accumulation Sachdeva, Robin RETINOPATIA DIABETICA ENFERMEDADES METABOLICAS HIPERGLUCEMIA |
title_short |
TRPC proteins contribute to development of diabetic retinopathy and regulate glyoxalase 1 activity and methylglyoxal accumulation |
title_full |
TRPC proteins contribute to development of diabetic retinopathy and regulate glyoxalase 1 activity and methylglyoxal accumulation |
title_fullStr |
TRPC proteins contribute to development of diabetic retinopathy and regulate glyoxalase 1 activity and methylglyoxal accumulation |
title_full_unstemmed |
TRPC proteins contribute to development of diabetic retinopathy and regulate glyoxalase 1 activity and methylglyoxal accumulation |
title_sort |
TRPC proteins contribute to development of diabetic retinopathy and regulate glyoxalase 1 activity and methylglyoxal accumulation |
dc.creator.none.fl_str_mv |
Sachdeva, Robin Schlotterer, Andrea Schumacher, Dagmar Matka, Christin Mathar, Ilka Dietrich, Nadine Medert, Rebekka Kriebs, Ulrich Lin, Jihong Nawroth, Peter Birnbaumer, Lutz Fleming, Thomas Freichel, Marc Hammes, Hans Peter |
author |
Sachdeva, Robin |
author_facet |
Sachdeva, Robin Schlotterer, Andrea Schumacher, Dagmar Matka, Christin Mathar, Ilka Dietrich, Nadine Medert, Rebekka Kriebs, Ulrich Lin, Jihong Nawroth, Peter Birnbaumer, Lutz Fleming, Thomas Freichel, Marc Hammes, Hans Peter |
author_role |
author |
author2 |
Schlotterer, Andrea Schumacher, Dagmar Matka, Christin Mathar, Ilka Dietrich, Nadine Medert, Rebekka Kriebs, Ulrich Lin, Jihong Nawroth, Peter Birnbaumer, Lutz Fleming, Thomas Freichel, Marc Hammes, Hans Peter |
author2_role |
author author author author author author author author author author author author author |
dc.subject.none.fl_str_mv |
RETINOPATIA DIABETICA ENFERMEDADES METABOLICAS HIPERGLUCEMIA |
topic |
RETINOPATIA DIABETICA ENFERMEDADES METABOLICAS HIPERGLUCEMIA |
dc.description.none.fl_txt_mv |
Fil: Sachdeva, Robin. Heidelberg Universit. Institute of Pharmacology; Alemania Fil: Schlotterer, Andrea. Heidelberg Universit. Medical Faculty Mannheim. Vth Department of Medicine; Alemania Fil: Schumacher, Dagmar. Heidelberg Universit. Institute of Pharmacology; Alemania Fil: Matka, Christin. Heidelberg Universit. Institute of Pharmacology; Alemania Fil: Mathar, Ilka. Heidelberg Universit. Institute of Pharmacology; Alemania Fil: Dietrich, Nadine. Heidelberg Universit. Medical Faculty Mannheim. Vth Department of Medicine; Alemania Fil: Medert, Rebekka. Heidelberg Universit. Institute of Pharmacology; Alemania Fil: Kriebs, Ulrich. Heidelberg Universit. Institute of Pharmacology; Alemania Fil: Lin, Jihong. Heidelberg Universit. Medical Faculty Mannheim. Vth Department of Medicine; Alemania Fil: Nawroth, Peter. University Hospital Heidelberg. Department of Medicine I and Clinical Chemistry; Alemania Fil: Nawroth, Peter. German Center for Diabetes Research; Alemania Fil: Nawroth, Peter. Institute for Diabetes and Cancer IDC Helmholtz Center Munich; Alemania Fil: Nawroth, Peter. eidelberg University Hospital. Departament of Medicine I. Joint Heidelberg Institute for Diabetes and Cancer Translational Diabetes Program; Alemania Fil: Birnbaumer, Lutz. National Institute of Environmental Health Sciences. Neurobiology Laboratoy; Estados Unidos Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Hammes, Hans-Peter. Heidelberg Universit. Medical Faculty Mannheim. Vth Department of Medicine; Alemania Fil: Freichel, Marc. Heidelberg Universit. Institute of Pharmacology; Alemania Objective Diabetic retinopathy (DR) is induced by an accumulation of reactive metabolites such as ROS, RNS, and RCS species, which were reported to modulate the activity of cation channels of the TRPC family. In this study, we use Trpc1/4/5/6−/− compound knockout mice to analyze the contribution of these TRPC proteins to diabetic retinopathy. Methods We used Nanostring- and qPCR-based analysis to determine mRNA levels of TRPC channels in control and diabetic retinae and retinal cell types. Chronic hyperglycemia was induced by Streptozotocin (STZ) treatment. To assess the development of diabetic retinopathy, vasoregression, pericyte loss, and thickness of individual retinal layers were analyzed. Plasma and cellular methylglyoxal (MG) levels, as well as Glyoxalase 1 (GLO1) enzyme activity and protein expression, were measured in WT and Trpc1/4/5/6−/− cells or tissues. MG-evoked toxicity in cells of both genotypes was compared by MTT assay. Results: We find that Trpc1/4/5/6−/− mice are protected from hyperglycemia-evoked vasoregression determined by the formation of acellular capillaries and pericyte drop-out. In addition, Trpc1/4/5/6−/− mice are resistant to the STZ-induced reduction in retinal layer thickness. The RCS metabolite methylglyoxal, which represents a key mediator for the development of diabetic retinopathy, was significantly reduced in plasma and red blood cells (RBCs) of STZ-treated Trpc1/4/5/6−/− mice compared to controls. GLO1 is the major MG detoxifying enzyme, and its activity and protein expression were significantly elevated in Trpc1/4/5/6-deficient cells, which led to significantly increased resistance to MG toxicity. GLO1 activity was also increased in retinal extracts from Trpc1/4/5/6−/− mice. The TRPCs investigated here are expressed at different levels in endothelial and glial cells of the retina. Conclusion The protective phenotype in diabetic retinopathy observed in Trpc1/4/5/6−/− mice is suggestive of a predominant action of TRPCs in Müller cells and microglia because of their central position in the retention of a proper homoeostasis of the neurovascular unit. |
description |
Fil: Sachdeva, Robin. Heidelberg Universit. Institute of Pharmacology; Alemania |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
https://repositorio.uca.edu.ar/handle/123456789/8705 2212-8778 10.1016/j.molmet.2018.01.003 29373286 Sachdeva R, Schlotterer A, Schumacher D, et al. TRPC proteins contribute to development of diabetic retinopathy and regulate glyoxalase 1 activity and methylglyoxal accumulation [en línea]. Molecular Metabolism. 2018;9:156-167. doi:10.1016/j.molmet.2018.01.003 Disponible en: |
url |
https://repositorio.uca.edu.ar/handle/123456789/8705 |
identifier_str_mv |
2212-8778 10.1016/j.molmet.2018.01.003 29373286 Sachdeva R, Schlotterer A, Schumacher D, et al. TRPC proteins contribute to development of diabetic retinopathy and regulate glyoxalase 1 activity and methylglyoxal accumulation [en línea]. Molecular Metabolism. 2018;9:156-167. doi:10.1016/j.molmet.2018.01.003 Disponible en: |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/4.0/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/4.0/ |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
dc.source.none.fl_str_mv |
Molecular Metabolism. 2018;9:156-167 reponame:Repositorio Institucional (UCA) instname:Pontificia Universidad Católica Argentina |
reponame_str |
Repositorio Institucional (UCA) |
collection |
Repositorio Institucional (UCA) |
instname_str |
Pontificia Universidad Católica Argentina |
repository.name.fl_str_mv |
Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentina |
repository.mail.fl_str_mv |
claudia_fernandez@uca.edu.ar |
_version_ |
1836638347525619712 |
score |
13.22299 |