Role of ER stress in hypoglycemia-induced mouse retina cell death.

Details

Serval ID
serval:BIB_1ED80AC0BD49
Type
Proceedings: the proceedings of a conference.
Collection
Publications
Institution
Title
Role of ER stress in hypoglycemia-induced mouse retina cell death.
Organization
EASDec Meeting 2019, Amsterdam, Holland
Issued date
16/05/2019
Editor
Roduit Raphael
Language
english
Abstract
Glucose is one of the most important metabolic substrates of the retina and maintenance of normoglycemia is an essential challenge for diabetic patients. Glycemic excursions could lead to serious side effects, including retinopathy. A vast body of literature exists on hyperglycemia especially in the field of diabetic retinopathy, but very little is known about the deleterious effect of hypoglycemia. When the cells are in hypoglycemic conditions, several pathways can be triggered: apoptosis, autophagy, and pathways linked to endoplasmic reticulum (ER) stress. We recently showed that hypoglycemia-induced retinal cell death in mouse implies the glutathione (GSH) scavenger protein. In addition, low glucose conditions are associated with autophagy defects in 661W photoreceptor cells and retinal explants.
In order to study ER stress in hypoglycemic conditions, we cultured 661W photoreceptor cells and retinal explants in diverse (1mM/25mM) glucose conditions and analyzed ER stress markers by qPCR and Western Blot analysis.
Using thapsigargin (an ER stress activator) as control, we first show the cleavage of XBP1 and the upregulation of many ER stress genes (BIP, CHOP, ATF4 and 6) at mRNA and protein levels when 661W cells were cultured in low glucose conditions. As low glucose induces a reduction of GSH level, we tested the role of GSH alone, using an inhibitor of its synthesis. No ER stress was detectable when GSH is chemically decreased (to 20%) by buthionine sulfoximine (BSO), suggesting that GSH is not implicated in low glucose-generated ER stress.
A better understanding of the molecular mechanisms induced by hypoglycemia that trigger cell death, autophagy defects and ER stress may lead to new ways of preventing retinal degeneration and decreased eyesight in diabetes.
Create date
06/11/2020 9:29
Last modification date
07/11/2020 6:26
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