Neutral Ceramidase Secreted Via Exosome Protects Against Palmitate-Induced Apoptosis in INS-1 Cells

S. Tang; F. Luo; Y. M. Feng; X. Wei; H. Miao; Y. B. Lu; Y. Tang; D. F. Ding; J. F. Jin; Q. Zhu

doi:10.1055/s-0042-116314

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2017; 125(02): 130-135
DOI: 10.1055/s-0042-116314

Article

Neutral Ceramidase Secreted Via Exosome Protects Against Palmitate-Induced Apoptosis in INS-1 Cells

S. Tang^*

¹Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China

,

F. Luo^*

¹Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China

,

Y. M. Feng^*

¹Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China

,

X. Wei

²Endocrine 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

,

H. Miao

¹Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China

,

Y. B. Lu

¹Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China

,

Y. Tang

¹Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China

,

D. F. Ding

¹Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China

,

J. F. Jin

³China-USA Lipids in Health and Disease Research Center, Guilin Medical University, Guilin, China

,

Q. Zhu

¹Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China

⁴Department of Emergency, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China

› Author Affiliations

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.

Key words

neutral ceramidase - exosome - lipotoxicity - β-cell - type 2 diabetes

Full Text

References

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