Melatonin Suppresses Apoptosis of Nucleus Pulposus Cells through Inhibiting Autophagy via the PI3K/Akt Pathway in a High-Glucose Culture.

Abstract

Diabetes mellitus- (DM-) associated hyperglycemia promotes apoptosis of disc nucleus pulposus (NP) cells, which is a contributor to intervertebral disc degeneration (IDD). Melatonin is able to protect against cell apoptosis. However, its effects on apoptosis of NP cell in a high-glucose culture remain unclear. The purpose of the present study was to investigate the effects and molecular mechanism of melatonin on NP cell apoptosis in a high-glucose culture. NP cells were cultured in the baseline medium supplemented with a high-glucose concentration (0.2 M) for 3 days. The control cells were only cultured in the baseline medium. Additionally, the pharmaceutical inhibitor LY294002 was added along with the culture medium to investigate the possible role of the PI3K/Akt pathway. Apoptosis, autophagy, and activity of the PI3K/Akt pathway of NP cells among these groups were evaluated. Compared with the control NP cells, high glucose significantly increased cell apoptosis ratio and caspase-3/caspase-9 activity and decreased mRNA expression of Bcl-2, whereas it increased mRNA or protein expression of Bax, caspase-3, cleaved caspase-3, cleaved PARP, and autophagy-related molecules (Atg3, Atg5, Beclin-1, and LC3-II) and decreased protein expression of p-Akt compared with the control cells. Additionally, melatonin partly inhibited the effects of high glucose on those parameters of cell apoptosis, autophagy, and activation of PI3K/Akt. In conclusion, melatonin attenuates apoptosis of NP cells through inhibiting the excessive autophagy via the PI3K/Akt pathway in a high-glucose culture. This study provides new theoretical basis of the protective effects of melatonin against disc degeneration in a DM patient.

• Authors: Jian Li, Chengqiang Wang, Lixin Xue, Fan Zhang, Jianqiang Liu
• Journal: BioMed research international (Biomed Res Int) Vol. 2021 Pg. 4604258 ( 2021) ISSN: 2314-6141 [Electronic] United States
• PMID: 34660789 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Jian Li et al.

Chemical References

• Central Nervous System Depressants
• Sweetening Agents
• Proto-Oncogene Proteins c-akt
• Glucose
• Melatonin

Topics

• Animals
• Apoptosis
• Autophagy
• Cells, Cultured
• Central Nervous System Depressants (pharmacology)
• Glucose (toxicity)
• Melatonin (pharmacology)
• Nucleus Pulposus (drug effects, metabolism, pathology)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Rats
• Signal Transduction
• Sweetening Agents (toxicity)