Spermidine prevents high glucose‐induced senescence in HT‐22 cells by upregulation of CB1 receptor

• Published in: Clinical and experimental pharmacology & physiology 2018-08, Vol.45 (8), p.832-840
• Main Authors: Zhu, Wei‐Wen, Xiao, Fan, Tang, Yi‐Yun, Zou, Wei, Li, Xiang, Zhang, Ping, Wang, Ai‐Ping, Tang, Xiao‐Qing
• Format: Article
• Language: English
• Subjects: Aging; Cannabinoid CB1 receptors; CB1 receptor; Cholecystokinin; Cyclin-dependent kinase inhibitor p21; Diabetes; Diabetes mellitus; diabetic encephalopathy; Diabetic neuropathy; Encephalopathy; Galactosidase; Glucose; high glucose; hyperglyceamia; Hyperglycemia; INK4a protein; Neuroprotection; Neurotoxicity; p16 Protein; Pathogenesis; Senescence; Spermidine; Up-regulation; β-Galactosidase
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/1440-1681.12955

Summary Hyperglycaemia‐induced neurotoxicity involved in the pathogenesis of diabetic encephalopathy and neuronal senescence is one of the worst effects of hyperglyceamic neurotoxicity. Cannabinoid receptor type 1 (CB1) has neuroprotective function in a series of neuropathy. Spermidine (Spd) has anti‐aging function in many tissues. However, the role of Spd in hyperglyceamia‐induced neuronal senescence remains unexplored. Therefore, we used high glucose (HG)‐treated HT‐22 cell as vitro model to investigate whether Spd protects neurons against hyperglyceamia‐induced senescence and the mediatory role of CB1 receptor. The HT‐22 cells were cultured in HG condition in the presence of different dose of Spd. Then, the viability of cells was measured by Cell Counting Kit‐8 (CCK‐8) assay. The senescence of cells was detected by Senescence‐associated β‐galactosidase (SA‐β‐Gal) staining. The expressions of p16INK4a, p21CIP1 and CB1 receptor were measured by western blot. We found that Spd inhibited HG‐induced neurotoxicity (the loss of cell viability) and senescence (the increase of SA‐β‐Gal positive cells, the upregulation of p16INK4a and p21CIP1) in HT‐22 cells. Also, Spd prevented HG‐induced downregulation of CB1 receptor in HT‐22 cells. Furthermore, we demonstrated that AM251 (a specific inhibitor of the CB1 receptor) reversed the protective effects of Spd on HG‐induced neurotoxicity and senescence. These results indicated that Spd prevents HG‐induced neurotoxicity and senescence via the upregulation of CB1 receptor. Our findings provide a promising future of Spd‐based preventions and therapies for diabetic encephalopathy.