PMID- 28674283 OWN - NLM STAT- MEDLINE DCOM- 20180511 LR - 20180511 IS - 1348-4540 (Electronic) IS - 0918-8959 (Linking) VI - 64 IP - 8 DP - 2017 Aug 30 TI - Neutral ceramidase activity inhibition is involved in palmitate-induced apoptosis in INS-1 cells. PG - 767-776 LID - 10.1507/endocrj.EJ16-0512 [doi] AB - 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 beta 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. FAU - Luo, Fen AU - Luo F AD - Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China. FAU - Feng, Yamin AU - Feng Y AD - Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China. FAU - Ma, Huimin AU - Ma H AD - Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China. FAU - Liu, Chao AU - Liu C AD - 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. FAU - Chen, Guofang AU - Chen G AD - 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. FAU - Wei, Xiao AU - Wei X AD - 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. FAU - Mao, Xiaodong AU - Mao X AD - 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. FAU - Li, Xingjia AU - Li X AD - 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. FAU - Xu, Yijiao AU - Xu Y AD - 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. FAU - Tang, Shan AU - Tang S AD - Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China. FAU - Wen, Honghua AU - Wen H AD - Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China. FAU - Jin, Junfei AU - Jin J AD - China-USA Lipids in Health and Disease Research Center, Guilin Medical University, Gulin 541001, China. FAU - Zhu, Qun AU - Zhu Q AD - Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China. LA - eng PT - Journal Article DEP - 20170701 PL - Japan TA - Endocr J JT - Endocrine journal JID - 9313485 RN - 2V16EO95H1 (Palmitic Acid) RN - EC 3.5.1.23 (Neutral Ceramidase) SB - IM MH - Animals MH - Apoptosis/*drug effects MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Down-Regulation/drug effects MH - Insulin-Secreting Cells/cytology/*drug effects/enzymology MH - Neutral Ceramidase/*metabolism MH - Palmitic Acid/*pharmacology MH - Pancreas/cytology/*drug effects/enzymology MH - Rats OTO - NOTNLM OT - Apoptosis OT - Ceramide OT - Neutral ceramidase OT - Palmitate OT - Pancreatic beta-cells EDAT- 2017/07/05 06:00 MHDA- 2018/05/12 06:00 CRDT- 2017/07/05 06:00 PHST- 2017/07/05 06:00 [pubmed] PHST- 2018/05/12 06:00 [medline] PHST- 2017/07/05 06:00 [entrez] AID - 10.1507/endocrj.EJ16-0512 [doi] PST - ppublish SO - Endocr J. 2017 Aug 30;64(8):767-776. doi: 10.1507/endocrj.EJ16-0512. Epub 2017 Jul 1.