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SIRT1 inhibits apoptosis in in vivo and in vitro models of spinal cord injury via microRNA-494.

Abstract
The aim of the present study was to investigate the function and mechanism of sirtuin 1 (SIRT1) in spinal cord injury (SCI). Reverse transcription‑quantitative polymerase chain reaction was used to measure the expression levels of microRNA (miR)‑494. MTT assay, lactate dehydrogenase activity assay and flow cytometry were used to analyze the effects of miR‑494 on cell growth and apoptosis in a model of SCI. The present study demonstrated that SIRT1 expression was reduced; whereas miR‑494 expression was increased in a rat model of SCI. Overexpression of miR‑494 suppressed the protein expression levels of SIRT1, and induced p53 protein expression. Conversely, knockdown of miR‑494 induced SIRT1 protein expression in an in vitro model of SCI. Furthermore, overexpression of miR‑494 promoted cell apoptosis and decreased cell growth in an in vitro model of SCI; however, miR‑494 knockdown enhanced cell growth and inhibited cell apoptosis. Administration of a SIRT1 agonist reduced the effects of miR‑494 overexpression on cell apoptosis in an SCI model, whereas treatment with a p53 agonist reduced the effects of miR‑494 knockdown on cell apoptosis in an SCI model. Together, these findings suggested that SIRT1 may inhibit apoptosis of SCI in vivo and in vitro through the p53 signaling pathway, whereas miR‑494 suppressed SIRT1 and induced apoptosis.
AuthorsXiaobing Yu, Shuo Zhang, Dewei Zhao, Xiuzhi Zhang, Chongjun Xia, Tienan Wang, Meng Zhang, Tao Liu, Wei Huang, Baolin Wu
JournalInternational journal of molecular medicine (Int J Mol Med) Vol. 43 Issue 4 Pg. 1758-1768 (Apr 2019) ISSN: 1791-244X [Electronic] Greece
PMID30816451 (Publication Type: Journal Article)
Chemical References
  • Lipopolysaccharides
  • MIRN494 microRNA, rat
  • MicroRNAs
  • Tumor Suppressor Protein p53
  • Sirtuin 1
Topics
  • Animals
  • Apoptosis (genetics)
  • Base Sequence
  • Disease Models, Animal
  • Lipopolysaccharides (pharmacology)
  • Male
  • MicroRNAs (genetics, metabolism)
  • Models, Biological
  • PC12 Cells
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction (drug effects)
  • Sirtuin 1 (metabolism)
  • Spinal Cord Injuries (genetics, metabolism, pathology)
  • Tumor Suppressor Protein p53 (agonists, metabolism)

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