High Glucose-Induced Apoptosis Is Linked to Mitochondrial Connexin 43 Level in RRECs: Implications for Diabetic Retinopathy

Diabetic retinopathy (DR) is one of the most common causes of vision loss and blindness among the working-age population. High glucose (HG)-induced decrease in mitochondrial connexin 43 (mtCx43) level is known to promote mitochondrial fragmentation, cytochrome c release, and apoptosis in retinal end...

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Autores principales: Aravind Sankaramoorthy, Sayon Roy
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/4c7990f116e043e79ca8215657586abf
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spelling oai:doaj.org-article:4c7990f116e043e79ca8215657586abf2021-11-25T17:11:32ZHigh Glucose-Induced Apoptosis Is Linked to Mitochondrial Connexin 43 Level in RRECs: Implications for Diabetic Retinopathy10.3390/cells101131022073-4409https://doaj.org/article/4c7990f116e043e79ca8215657586abf2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3102https://doaj.org/toc/2073-4409Diabetic retinopathy (DR) is one of the most common causes of vision loss and blindness among the working-age population. High glucose (HG)-induced decrease in mitochondrial connexin 43 (mtCx43) level is known to promote mitochondrial fragmentation, cytochrome c release, and apoptosis in retinal endothelial cells associated with DR. In this study, we investigated whether counteracting HG-induced decrease in mtCx43 level would preserve mitochondrial integrity and prevent apoptosis. Rat retinal endothelial cells (RRECs) were grown in normal (N; 5 mM glucose) or HG (30 mM glucose) medium for 7 days. In parallel, cells grown in HG were transfected with Cx43 plasmid, or empty vector (EV), as control. Western blot (WB) analysis showed a significant decrease in mtCx43 level concomitant with increased cleaved caspase-3, Bax, cleaved PARP, and mitochondrial fragmentation in cells grown in HG condition compared to those grown in N medium. When cells grown in HG were transfected with Cx43 plasmid, mtCx43 level was significantly increased and resulted in reduced cleaved caspase-3, Bax, cleaved PARP and preservation of mitochondrial morphology with a significant decrease in the number of TUNEL-positive cells compared to those grown in HG alone. Findings from the study indicate a novel role for mtCx43 in regulating apoptosis and that maintenance of mtCx43 level could be useful in preventing HG-induced apoptosis by reducing mitochondrial fragmentation associated with retinal vascular cell loss in DR.Aravind SankaramoorthySayon RoyMDPI AGarticlehigh glucoseapoptosismitochondrial connexin 43endothelial cellsdiabetic retinopathyBiology (General)QH301-705.5ENCells, Vol 10, Iss 3102, p 3102 (2021)
institution DOAJ
collection DOAJ
language EN
topic high glucose
apoptosis
mitochondrial connexin 43
endothelial cells
diabetic retinopathy
Biology (General)
QH301-705.5
spellingShingle high glucose
apoptosis
mitochondrial connexin 43
endothelial cells
diabetic retinopathy
Biology (General)
QH301-705.5
Aravind Sankaramoorthy
Sayon Roy
High Glucose-Induced Apoptosis Is Linked to Mitochondrial Connexin 43 Level in RRECs: Implications for Diabetic Retinopathy
description Diabetic retinopathy (DR) is one of the most common causes of vision loss and blindness among the working-age population. High glucose (HG)-induced decrease in mitochondrial connexin 43 (mtCx43) level is known to promote mitochondrial fragmentation, cytochrome c release, and apoptosis in retinal endothelial cells associated with DR. In this study, we investigated whether counteracting HG-induced decrease in mtCx43 level would preserve mitochondrial integrity and prevent apoptosis. Rat retinal endothelial cells (RRECs) were grown in normal (N; 5 mM glucose) or HG (30 mM glucose) medium for 7 days. In parallel, cells grown in HG were transfected with Cx43 plasmid, or empty vector (EV), as control. Western blot (WB) analysis showed a significant decrease in mtCx43 level concomitant with increased cleaved caspase-3, Bax, cleaved PARP, and mitochondrial fragmentation in cells grown in HG condition compared to those grown in N medium. When cells grown in HG were transfected with Cx43 plasmid, mtCx43 level was significantly increased and resulted in reduced cleaved caspase-3, Bax, cleaved PARP and preservation of mitochondrial morphology with a significant decrease in the number of TUNEL-positive cells compared to those grown in HG alone. Findings from the study indicate a novel role for mtCx43 in regulating apoptosis and that maintenance of mtCx43 level could be useful in preventing HG-induced apoptosis by reducing mitochondrial fragmentation associated with retinal vascular cell loss in DR.
format article
author Aravind Sankaramoorthy
Sayon Roy
author_facet Aravind Sankaramoorthy
Sayon Roy
author_sort Aravind Sankaramoorthy
title High Glucose-Induced Apoptosis Is Linked to Mitochondrial Connexin 43 Level in RRECs: Implications for Diabetic Retinopathy
title_short High Glucose-Induced Apoptosis Is Linked to Mitochondrial Connexin 43 Level in RRECs: Implications for Diabetic Retinopathy
title_full High Glucose-Induced Apoptosis Is Linked to Mitochondrial Connexin 43 Level in RRECs: Implications for Diabetic Retinopathy
title_fullStr High Glucose-Induced Apoptosis Is Linked to Mitochondrial Connexin 43 Level in RRECs: Implications for Diabetic Retinopathy
title_full_unstemmed High Glucose-Induced Apoptosis Is Linked to Mitochondrial Connexin 43 Level in RRECs: Implications for Diabetic Retinopathy
title_sort high glucose-induced apoptosis is linked to mitochondrial connexin 43 level in rrecs: implications for diabetic retinopathy
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/4c7990f116e043e79ca8215657586abf
work_keys_str_mv AT aravindsankaramoorthy highglucoseinducedapoptosisislinkedtomitochondrialconnexin43levelinrrecsimplicationsfordiabeticretinopathy
AT sayonroy highglucoseinducedapoptosisislinkedtomitochondrialconnexin43levelinrrecsimplicationsfordiabeticretinopathy
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