title: Neutral Ceramidase Secreted Via Exosome Protects Against Palmitate-Induced Apoptosis in INS-1 Cells.
abstract: Aims:To investigate the effects of neutral ceramidase (NCDase) packaged in exosomes that are secreted from β-cells on free fatty acid (FFA)-induced β-cells apoptosis and its role in regulation of sphingolipid-mediated signaling pathway.Methods:HPLC and Western blotting were performed to determine NCDase activity and expression. Annexin V-fluorescein-isothiocyanate/propidium iodide flow cytometry was used to assess apoptosis. Electrospray ionization tandem mass spectrometry was used for ceramide (Cer), sphingosine-1-phosphate (S1P), and sphingosine (SPH) determination.Results:INS-1 cells over-expressed NCDase secreted active NCDase via exosomes. Exosomes isolated from the cultured medium of INS-1 cells that oxpressed NCDase could ameliorate palmitate-induced apoptosis. Furthermore, the results showed that exosome-derived NCDase treatment reduced intracellular Cer/S1P ratio.Conclusions:β-cell secreted active NCDase via exosome, the exosome-packaged-NCDase protected β-cells from FFA-induced apoptosis through regulating sphingolipid metabolites and it might be a potential treatment for β-cell lipotoxicity and type 2 diabetes.
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: S
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: F
authors.initials: F
authors.lastname: Luo
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Y M
authors.initials: YM
authors.lastname: Feng
authors.affiliation: 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, China.
authors.forename: X
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: H
authors.initials: H
authors.lastname: Miao
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Y B
authors.initials: YB
authors.lastname: Lu
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: D F
authors.initials: DF
authors.lastname: Ding
authors.affiliation: China-USA Lipids in Health and Disease Research Center, Guilin Medical University, Guilin, China.
authors.forename: J F
authors.initials: JF
authors.lastname: Jin
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D055354:Exosomes / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D055576:Neutral Ceramidase / Q000378:metabolism*; D019308:Palmitic Acid / Q000633:toxicity*; D051381:Rats; D013107:Sphingolipids / Q000378:metabolism
chemical_list: D013107:Sphingolipids; D019308:Palmitic Acid; D055576:Neutral Ceramidase