Autophagy defect is associated with low glucose-induced apoptosis in 661W photoreceptor cells.

Glucose is an important metabolic substrate of the retina and diabetic patients have to maintain a strict normoglycemia to avoid diabetes secondary effects, including cardiovascular disease, nephropathy, neuropathy and retinopathy. Others and we recently demonstrated the potential role of hypoglycem...

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Autores principales:	Delphine Balmer, Martine Emery, Pénélope Andreux, Johan Auwerx, Vanessa Ginet, Julien Puyal, Daniel F Schorderet, Raphaël Roduit
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/92fdd53aac3d47d496ad86f7c7419976
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spelling	oai:doaj.org-article:92fdd53aac3d47d496ad86f7c74199762021-11-18T08:55:07ZAutophagy defect is associated with low glucose-induced apoptosis in 661W photoreceptor cells.1932-620310.1371/journal.pone.0074162https://doaj.org/article/92fdd53aac3d47d496ad86f7c74199762013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24066113/?tool=EBIhttps://doaj.org/toc/1932-6203Glucose is an important metabolic substrate of the retina and diabetic patients have to maintain a strict normoglycemia to avoid diabetes secondary effects, including cardiovascular disease, nephropathy, neuropathy and retinopathy. Others and we recently demonstrated the potential role of hypoglycemia in diabetic retinopathy. We showed acute hypoglycemia to induce retinal cell death both in vivo during an hyperinsulinemic/hypoglycemic clamp and in vitro in 661W photoreceptor cells cultured at low glucose concentration. In the present study, we showed low glucose to induce a decrease of BCL2 and BCL-XL anti-apoptotic proteins expression, leading to an increase of free pro-apoptotic BAX. In parallel, we showed that, in retinal cells, low glucose-induced apoptosis is involved in the process of autophagosomes formation through the AMPK/RAPTOR/mTOR pathway. Moreover, the decrease of LAMP2a expression led to a defect in the autophagosome/lysosome fusion process. Specific inhibition of autophagy, either by 3-methyladenine or by down-regulation of ATG5 or ATG7 proteins expression, increased caspase 3 activation and 661W cell death. We show that low glucose modifies the delicate equilibrium between apoptosis and autophagy. Cells struggled against low nutrient condition-induced apoptosis by starting an autophagic process, which led to cell death when inhibited. We conclude that autophagy defect is associated with low glucose-induced 661W cells death that could play a role in diabetic retinopathy. These results could modify the way of addressing negative effects of hypoglycemia. Short-term modulation of autophagy could be envisioned to treat diabetic patients in order to avoid secondary complications of the disease.Delphine BalmerMartine EmeryPénélope AndreuxJohan AuwerxVanessa GinetJulien PuyalDaniel F SchorderetRaphaël RoduitPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e74162 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Delphine Balmer Martine Emery Pénélope Andreux Johan Auwerx Vanessa Ginet Julien Puyal Daniel F Schorderet Raphaël Roduit Autophagy defect is associated with low glucose-induced apoptosis in 661W photoreceptor cells.
description	Glucose is an important metabolic substrate of the retina and diabetic patients have to maintain a strict normoglycemia to avoid diabetes secondary effects, including cardiovascular disease, nephropathy, neuropathy and retinopathy. Others and we recently demonstrated the potential role of hypoglycemia in diabetic retinopathy. We showed acute hypoglycemia to induce retinal cell death both in vivo during an hyperinsulinemic/hypoglycemic clamp and in vitro in 661W photoreceptor cells cultured at low glucose concentration. In the present study, we showed low glucose to induce a decrease of BCL2 and BCL-XL anti-apoptotic proteins expression, leading to an increase of free pro-apoptotic BAX. In parallel, we showed that, in retinal cells, low glucose-induced apoptosis is involved in the process of autophagosomes formation through the AMPK/RAPTOR/mTOR pathway. Moreover, the decrease of LAMP2a expression led to a defect in the autophagosome/lysosome fusion process. Specific inhibition of autophagy, either by 3-methyladenine or by down-regulation of ATG5 or ATG7 proteins expression, increased caspase 3 activation and 661W cell death. We show that low glucose modifies the delicate equilibrium between apoptosis and autophagy. Cells struggled against low nutrient condition-induced apoptosis by starting an autophagic process, which led to cell death when inhibited. We conclude that autophagy defect is associated with low glucose-induced 661W cells death that could play a role in diabetic retinopathy. These results could modify the way of addressing negative effects of hypoglycemia. Short-term modulation of autophagy could be envisioned to treat diabetic patients in order to avoid secondary complications of the disease.
format	article
author	Delphine Balmer Martine Emery Pénélope Andreux Johan Auwerx Vanessa Ginet Julien Puyal Daniel F Schorderet Raphaël Roduit
author_facet	Delphine Balmer Martine Emery Pénélope Andreux Johan Auwerx Vanessa Ginet Julien Puyal Daniel F Schorderet Raphaël Roduit
author_sort	Delphine Balmer
title	Autophagy defect is associated with low glucose-induced apoptosis in 661W photoreceptor cells.
title_short	Autophagy defect is associated with low glucose-induced apoptosis in 661W photoreceptor cells.
title_full	Autophagy defect is associated with low glucose-induced apoptosis in 661W photoreceptor cells.
title_fullStr	Autophagy defect is associated with low glucose-induced apoptosis in 661W photoreceptor cells.
title_full_unstemmed	Autophagy defect is associated with low glucose-induced apoptosis in 661W photoreceptor cells.
title_sort	autophagy defect is associated with low glucose-induced apoptosis in 661w photoreceptor cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/92fdd53aac3d47d496ad86f7c7419976
work_keys_str_mv	AT delphinebalmer autophagydefectisassociatedwithlowglucoseinducedapoptosisin661wphotoreceptorcells AT martineemery autophagydefectisassociatedwithlowglucoseinducedapoptosisin661wphotoreceptorcells AT penelopeandreux autophagydefectisassociatedwithlowglucoseinducedapoptosisin661wphotoreceptorcells AT johanauwerx autophagydefectisassociatedwithlowglucoseinducedapoptosisin661wphotoreceptorcells AT vanessaginet autophagydefectisassociatedwithlowglucoseinducedapoptosisin661wphotoreceptorcells AT julienpuyal autophagydefectisassociatedwithlowglucoseinducedapoptosisin661wphotoreceptorcells AT danielfschorderet autophagydefectisassociatedwithlowglucoseinducedapoptosisin661wphotoreceptorcells AT raphaelroduit autophagydefectisassociatedwithlowglucoseinducedapoptosisin661wphotoreceptorcells
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Autophagy defect is associated with low glucose-induced apoptosis in 661W photoreceptor cells.

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