Involvement of oxidative stress and impaired lysosomal degradation in amiodarone-induced schwannopathy

作者：Niimi Naoko; Yako Hideji; Tsukamoto Masami; Takaku Shizuka; Yamauchi Junji; Kawakami Emiko; Yanagisawa Hiroko; Watabe Kazuhiko; Utsunomiya Kazunori; Sango Kazunori

来源：European Journal of Neuroscience, 2016, 44(1): 1723-1733.

DOI：10.1111/ejn.13268

• demyelination
• invitro
• neurotoxicology
• peripheral neuropathy
• Schwann cells

Amiodarone hydrochloride (AMD), an anti-arrhythmic agent, has been shown to cause peripheral neuropathy; however, its pathogenesis remains unknown. We examined the toxic effects of AMD on an immortalized adult rat Schwann cell line, IFRS1, and cocultures of IFRS1 cells and adult rat dorsal root ganglion neurons or nerve growth factor-primed PC12 cells. Treatment with AMD (1, 5, and 10m) induced time- and dose-dependent cell death, accumulation of phospholipids and neutral lipids, upregulation of the expression of gangliosides, and oxidative stress (increased nuclear factor E2-related factor in nuclear extracts and reduced GSH/GSSG ratios) in IFRS1 cells. It also induced the upregulation of LC3-II and p62 expression, with phosphorylation of p62, suggesting that deficient autolysosomal degradation is involved in AMD-induced IFRS1 cell death. Furthermore, treatment of the cocultures with AMD induced detachment of IFRS1 cells from neurite networks in a time- and dose-dependent manner. These findings suggest that AMD-induced lysosomal storage accompanied by enhanced oxidative stress and impaired lysosomal degradation in Schwann cells might be a cause of demyelination in the peripheral nervous system.

• 出版日期2016-7
• 单位河北医科大学