title: Effects of High Glucose on Cell Viability and Differentiation in Primary Cultured Schwann Cells: Potential Role of ERK Signaling Pathway.
abstract: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus and hyperglycemia is considered to be the major factor in the development and progression of DPN. Because of the contribution of Schwann cells (SCs) to the pathology of DPN, we investigated the effects of high glucose on cell proliferation, apoptosis and differentiation in primary cultured SCs. Cell Counting Kit-8 (CCK-8) assay and Hoechst staining showed that high glucose inhibited SCs proliferation and increased apoptosis ratio in time and concentration dependent manner. Western blot and real-time quantitative PCR analysis revealed that the major myelin proteins and genes expressions including P0, MAG and Krox-20, were downregulated time dependently in SCs exposed to high glucose from 48 to 96 h. To further elucidate the underlying pathogenic mechanisms, we also explored the role of ERK signaling pathway in high glucose induced SC injury, which has been proved to drive demyelination of peripheral nerves. The western blot analysis showed that compared with control group phosphorylation level of ERK was increased by 14.3 % in SCs exposed to high glucose for 72 h (P < 0.01). Using immunocytochemistry analysis, we observed that the ERK specific inhibitor U0126 blocked the ERK activation induced by high glucose and reversed the inhibitory effect of high glucose on P0 expression. Taken together, these results suggest that high glucose can cause damage in primary cultured SCs and may exert the inhibitory effect on SC differentiation and myelination through ERK signaling activation.
authors.affiliation: Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China. xcliang@vip.sina.com.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of cell resource center, Institute of Basic Medical Science, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005947:Glucose / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D061251:Primary Cell Culture / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000187:drug effects / Q000201:enzymology*
chemical_list: D005947:Glucose
keywords: Diabetic peripheral neuropathy; Differentiation; ERK signaling pathway; High glucose; Schwann cells