p66shc deficiency attenuates high glucose-induced autophagy dysfunction in Schwann cells

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Su-Jeong Choi Giang-Huong Vu Harsha Nagar Seonhee Kim Ikjun Lee Shuyu Piao Byeong Hwa Jeon Kaikobad Irani Sang-Ha Oh Cuk-Seong Kim
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제29권 제1호, 57~66쪽, 전체 10쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2025.01.01

국문 초록

Schwann cells are the most abundant cells in the peripheral nervous system, maintaining the development, function and regeneration of peripheral nerves. Defects in these Schwann cells injury response potentially contribute to the pathogenesis of diabetic peripheral neuropathy (DPN), a common complication of diabetes mellitus. The protein p66shc is essential in regulating oxidative stress responses, autophagy induction and cell survival, and is also vital in the development of DPN. In this study, we hypothesized that p66shc mediates high glucose-induced oxidative stress and autophagic dysfunction. In Schwann cells treated with high glucose; p66shc expression, levels of reactive oxygen species, autophagy impairment, and early apoptosis were elevated. Inhibition of p66shc gene expression by siRNA reversed high glucose-induced oxidative stress, autophagy impairment, and early apoptosis. We also demonstrated that the levels of p66shc was increased, while autophagy-related proteins p62 and LC3 (LC3-II/I) were suppressed in the sciatic nerve of streptozotocin-induced diabetes mice. P66shc-deficient mice exhibited the improvement in autophagy impairment after diabetes onset. Our findings suggest that the p66 plays a crucial role in Schwann cell dysfunction, identifying its potential as a therapeutic target.

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키워드

Autophagy Diabetic peripheral neuropathy Oxidative stress p66shc Schwann cells