Effects of thymosin β4 on oxygen‑glucose deprivation and reoxygenation‑induced injury

Int J Mol Med. 2018 Mar;41(3):1749-1755. doi: 10.3892/ijmm.2018.3369. Epub 2018 Jan 9.

Abstract

Cerebral ischemia causes severe brain injury and results in selective neuronal death through programmed cell death mechanisms, including apoptosis and autophagy. Minimizing neuronal injury has been considered a hot topic among clinicians. The present study elucidated the effect of thymosin β4 (Tβ4) on neuronal death induced by cerebral ischemia/reperfusion in PC12 cells that were subjected to oxygen‑glucose deprivation and reoxygenation (OGD/R). The survival, apoptotic and autophagy rates of PC12 cells were investigated. Tβ4 pre‑conditioning prior to OGD/R was performed to evaluate PC12‑cell viability and the protective mechanisms of Tβ4. Tβ4 significantly increased cell survival after OGD/R. Tβ4 inhibited the release of lactate dehydrogenase, downregulated malondialdehyde and upregulated the activities of glutathione peroxidase and superoxide dismutase. In addition, Tβ4 attenuated OGD/R‑associated decreases in the expression of P62 and the anti‑apoptotic protein B‑cell lymphoma‑2, as well as the upregulation of autophagy mediators, including autophagy‑related protein‑5 and the ratio of microtubule‑associated protein 1 light chain 3 (LC3) II vs. LC3 I. These results suggested that Tβ4 effectively inhibits cell apoptosis and autophagy induced by OGD/R. To the best of our knowledge, the present study was the first to report on the antioxidant, anti‑apoptotic and anti‑autophagic effects of Tβ4 in neuronal‑like PC12 cells. These results suggested that Tβ4 may be explored as a potential treatment for cerebral ischemia.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Autophagy / drug effects
  • Autophagy / genetics
  • Gene Expression Regulation / drug effects
  • Glucose / deficiency*
  • Glutathione Peroxidase / metabolism
  • L-Lactate Dehydrogenase
  • Malondialdehyde / metabolism
  • Oxygen / adverse effects*
  • PC12 Cells
  • Rats
  • Signal Transduction / drug effects
  • Superoxide Dismutase / metabolism
  • Thymosin / pharmacology*

Substances

  • Malondialdehyde
  • thymosin beta(4)
  • Thymosin
  • L-Lactate Dehydrogenase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glucose
  • Oxygen