Glycolaldehyde induces endoplasmic reticulum stress and apoptosis in Schwann cells

• Published in: Toxicology reports Vol. 2; no. C; pp. 1454 - 1462
• Main Authors: Sato, Keisuke, Tatsunami, Ryosuke, Yama, Kaori, Murao, Yu, Tampo, Yoshiko
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier 01.01.2015
• Subjects: Apoptosis; Endoplasmic reticulum stress; Glycolaldehyde; Nuclear factor E2-related factor 2; Schwann cell; AGEs, advanced glycation end products; ATF6, activating transcription factor 6; GA, glycolaldehyde; Glycolaldehyde; Nrf2, nuclear factor E2-related factor 2; Endoplasmic reticulum stress; MG, methylglyoxal; eIF2, eukaryotic initiation factor 2; Schwann cell; IRE1, inositol-requiring ER-to-nucleus signal kinase 1; CHOP, CCAAT/enhancer-binding homologous protein; PERK, RNA-dependent protein kinase-like ER kinase; ER, endoplasmic reticulum; HO-1, heme oxygenase-1; Nuclear factor E2-related factor 2; Apoptosis
• ISSN: 2214-7500; 2214-7500
• DOI: 10.1016/j.toxrep.2015.10.014

Schwann cell injury is caused by diabetic neuropathy. The apoptosis of Schwann cells plays a pivotal role in diabetic nerve dysfunction. Glycolaldehyde is a precursor of advanced glycation end products that contribute to the pathogenesis of diabetic neuropathy. In this study, we examined whether glycolaldehyde induces endoplasmic reticulum (ER) stress and apoptosis in rat Schwann cells. Schwann cells treated with 500 μM glycolaldehyde showed morphological changes characteristic of apoptosis. Glycolaldehyde activated apoptotic signals, such as caspase-3 and caspase-8. Furthermore, it induced ER stress response involving RNA-dependent protein kinase-like ER kinase (PERK), inositol-requiring ER-to-nucleus signal kinase 1α (IRE1α), and eukaryotic initiation factor 2α (eIF2α). In addition, glycolaldehyde activated CCAAT/enhancer-binding homologous protein (CHOP), an ER stress response factor crucial to executing apoptosis. Knockdown of nuclear factor E2-related factor 2 (Nrf2), which is involved in the promotion of cell survival following ER stress, enhanced glycolaldehyde-induced cytotoxicity, indicating that Nrf2 plays a protective role in the cytotoxicity caused by glycolaldehyde. Taken together, these findings indicate that glycolaldehyde is capable of inducing apoptosis and ER stress in Schwann cells. The ER stress induced by glycolaldehyde may trigger the glycolaldehyde-induced apoptosis in Schwann cells. This study demonstrated for the first time that glycolaldehyde induced ER stress.