Luo Fen, Feng Yamin, Ma Huimin, Liu Chao, Chen Guofang, Wei Xiao, Mao Xiaodong, Li Xingjia, Xu Yijiao, Tang Shan, Wen Honghua, Jin Junfei, Zhu Qun
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.
Endocr J. 2017 Aug 30;64(8):767-776. doi: 10.1507/endocrj.EJ16-0512. Epub 2017 Jul 1.
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.
中性神经酰胺酶（NCDase）是神经酰胺酶的一类，是神经酰胺降解中的关键酶。最近，有研究观察到饱和脂肪酸会抑制NCDase活性，从而增加大鼠肌肉中的神经酰胺含量。然而，关于其在棕榈酸（Palm）诱导的胰腺β细胞脂毒性中的活性变化和作用，我们却知之甚少。在此，我们证明了Palm处理可显著下调大鼠INS-1细胞中的NCDase活性、mRNA和蛋白水平。此外，Palm导致神经酰胺显著积累，而鞘氨醇（SPH）水平保持不变，这表明在用Palm处理24小时后，抑制NCDase活性不会导致SPH水平发生变化。此外，NCDase过表达显著降低了Palm诱导的INS-1细胞凋亡。相反，NCDase siRNA敲低显著加剧了Palm诱导的细胞凋亡。总之，Palm处理会抑制NCDase的活性，并下调其mRNA和蛋白表达。此外，NCDase抑制通过阻断INS-1细胞中的神经酰胺降解参与了Palm诱导的细胞凋亡。
