Glycolaldehyde Induces Cytotoxicity and Increases Glutathione and Multidrug-Resistance-Associated Protein Levels in Schwann Cells

Bali

Korean J Physiol Pharmacol

et al. 2014

1,144

794

During long standing hyperglycaemic state in diabetes mellitus, glucose forms covalent adducts with the plasma proteins through a non-enzymatic process known as glycation. Protein glycation and formation of advanced glycation end products (AGEs) play an important role in the pathogenesis of diabetic complications like retinopathy, nephropathy, neuropathy, cardiomyopathy along with some other diseases such as rheumatoid arthritis, osteoporosis and aging. Glycation of proteins interferes with their normal functions by disrupting molecular conformation, altering enzymatic activity, and interfering with receptor functioning. AGEs form intra- and extracellular cross linking not only with proteins, but with some other endogenous key molecules including lipids and nucleic acids to contribute in the development of diabetic complications. Recent studies suggest that AGEs interact with plasma membrane localized receptors for AGEs (RAGE) to alter intracellular signaling, gene expression, release of pro-inflammatory molecules and free radicals. The present review discusses the glycation of plasma proteins such as albumin, fibrinogen, globulins and collagen to form different types of AGEs. Furthermore, the role of AGEs in the pathogenesis of diabetic complications including retinopathy, cataract, neuropathy, nephropathy and cardiomyopathy is also discussed.

Section: Ages and Diabetic Complicationsmentioning

confidence: 99%

Advanced Glycation End Products and Diabetic Complications

Bali

Korean J Physiol Pharmacol

et al. 2014

1,144

794

“…There is only one report showing that GA induces apoptosis via oxidative stress in breast cancer cells [16] . On the other hand, we have reported that oxidative stress is not a major contributor to the GA-induced cytotoxicity in Schwann cells [12] . Endoplasmic reticulum (ER) stress was found to be involved in the induction of apoptosis that occurs in a wide range of metabolic diseases, including diabetes mellitus [17] .…”

Section: Introductionmentioning

confidence: 76%

“…It is reported that AGEs and MG induce apoptosis in Schwann cells [7] , [8] , [11] . In our previous report, we demonstrated that GA decreased the viability of rat Schwann cells [12] . Moreover, GA had a greater effect on Schwann cells than dicarbonyl compounds, such as MG.…”

Section: Introductionmentioning

confidence: 79%

See 1 more Smart Citation

Glycolaldehyde induces endoplasmic reticulum stress and apoptosis in Schwann cells

et al. 2015

Self Cite

Exp Clin Endocrinol Diabetes

“…AGEs were found in the peripheral nerves of diabetic rats, and the expression of RAGE was found in endothelial and Schwann cells, which may be responsible for impaired nerve function and pathological nerve alterations [26]. Glycolaldehyde (a precursor of AGEs) at physiological concentrations can decrease the viability of rat Schwann cells and thereby contribute to the pathogenesis and development of diabetic neuropathy [27].…”

Section: Introductionmentioning

confidence: 99%

Interleukin-10 Protects Schwann Cells against Advanced Glycation End Products-Induced Apoptosis via NF-κB Suppression

Bao²,

Men

et al. 2019

Demyelination resulting from Schwann cell injury is a main pathological feature of diabetic neuropathy, and a key contributor to this process may be inflammation due to advanced glycation end products (AGEs). Therefore, protection by anti-inflammation agents is anticipated. In this study, we showed that interleukin-10 (IL-10), an anti-inflammatory cytokine, inhibits apoptosis of Schwann cells induced by AGEs in vitro. We isolated and cultured Schwann cells from rat sciatic nerves. As detected by flow cytometry, apoptosis of Schwann cells markedly increased following incubation with AGEs for 48 h. However, pretreatment with IL-10 inhibited AGE-induced apoptosis. The effect of IL-10 on NF-κB, which is a very important regulator of inflammation, was also evaluated, and results showed high levels of phospho-NF-κB and nuclear localization of NF-κB in cells incubated with AGEs but low levels of phospho-NF-κB and cytoplasmic localization in the cells incubated with IL-10, indicating the activation of NF-κB by AGEs and inhibition of NF-κB by IL-10. Moreover, incubating Schwann cells with an NF-κB inhibitor (caffeic acid phenethyl ester) for 30 min before adding AGEs mimicked IL-10, lowering the amount of reactive oxygen species and activity of caspase-3 and also decreasing apoptosis in Schwann cells. These results indicate that IL-10 may protect Schwann cells against AGE-induced apoptosis by attenuating oxidative stress via the inhibition of activation of NF-κB.