1. Academic Validation
  2. Spermidine prevents high glucose-induced senescence in HT-22 cells by upregulation of CB1 receptor

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

  • Clin Exp Pharmacol Physiol. 2018 Aug;45(8):832-840. doi: 10.1111/1440-1681.12955.
Wei-Wen Zhu 1 2 Fan Xiao 1 2 3 Yi-Yun Tang 1 2 Wei Zou 1 3 Xiang Li 1 4 Ping Zhang 1 3 Ai-Ping Wang 1 5 Xiao-Qing Tang 1 2
Affiliations

Affiliations

  • 1 Institute of Neuroscience, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, China.
  • 2 Department of Physiology, Medical College, University of South China, Hengyang, Hunan, China.
  • 3 Department of Neurology, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan, China.
  • 4 Department of Anesthesiology, the First Affiliated Hospital, University of South China, Hengyang, Hunan, China.
  • 5 Department of Anatomy, Medical College, University of South China, Hengyang, Hunan, China.
Abstract

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.

Keywords

CB1 receptor; diabetic encephalopathy; high glucose; hyperglyceamia; senescence; spermidine.

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