Neutral ceramidase activity inhibition is involved in palmitate-induced apoptosis in INS-1 cells

Endocrine journal

Junfei Jin¹  Shan Tang²  Qun Zhu²  Huimin Ma²  Yamin Feng²  Honghua Wen²  Fen Luo²  Chao Liu³  Xiaodong Mao³  Xingjia Li³  Yijiao Xu³  Guofang Chen³  Xiao Wei³ 

[1] China-USA Lipids in Health and Disease Research Center, Guilin Medical University, Gulin 541001, China;Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China;Endocrine and Diabetes Center, Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing University of Traditional Chinese Medicine, Branch of China Academy of Chinese Medical Science, Nanjing 210028, China

关键词: Neutral ceramidase;    Palmitate;    Apoptosis;    Ceramide;    Pancreatic β    -cells;   

DOI  :  10.1507/endocrj.EJ16-0512

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

Neutral ceramidase (NCDase) is a class of ceramidases, a key enzyme in ceramide degradation.Recently, it was observed that NCDase activity was suppressed by saturated fatty acids to increase ceramide content in rat muscle.However, little is known about its changes in activity and roles in palmitate (Palm)-induced lipotoxicity in pancreatic β cells.Here, we demonstrated that Palm treatment significantly down-regulated NCDase activity, mRNA and protein levels in rat INS-1 cells.In addition, Palm caused a significant accumulation of ceramide, while SPH level remained unchanged, suggesting that inhibition of NCDase activity led to no change of SPH level after treatment with Palm for 24 h.Furthermore, NCDase overexpression significantly reduced Palm-induced apoptosis in INS-1 cells.Conversely, NCDase siRNA knockdown markedly exacerbated Palm-induced apoptosis.In conclusion, Palm treatment suppressed the activity of NCDase and down-regulated its mRNA and protein expression.Furthermore, NCDase inhibition was involved in Palm-induced apoptosis by blocking ceramide degradation in INS-1 cells.

【 授权许可】

Unknown