PMID- 33269749
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210703
IS  - 1673-5374 (Print)
IS  - 1876-7958 (Electronic)
IS  - 1673-5374 (Linking)
VI  - 16
IP  - 6
DP  - 2021 Jun
TI  - Apelin-13 inhibits apoptosis and excessive autophagy in cerebral 
      ischemia/reperfusion injury.
PG  - 1044-1051
LID - 10.4103/1673-5374.300725 [doi]
AB  - Apelin-13 is a novel endogenous ligand for an angiotensin-like orphan G-protein 
      coupled receptor, and it may be neuroprotective against cerebral ischemia injury. 
      However, the precise mechanisms of the effects of apelin-13 remain to be 
      elucidated. To investigate the effects of apelin-13 on apoptosis and autophagy in 
      models of cerebral ischemia/reperfusion injury, a rat model was established by 
      middle cerebral artery occlusion. Apelin-13 (50 mug/kg) was injected into the 
      right ventricle as a treatment. In addition, an SH-SY5Y cell model was 
      established by oxygen-glucose deprivation/reperfusion, with cells first cultured 
      in sugar-free medium with 95% N(2) and 5% CO(2) for 4 hours and then cultured in 
      a normal environment with sugar-containing medium for 5 hours. This SH-SY5Y cell 
      model was treated with 10(-7) M apelin-13 for 5 hours. Results showed that 
      apelin-13 protected against cerebral ischemia/reperfusion injury. Apelin-13 
      treatment alleviated neuronal apoptosis by increasing the ratio of Bcl-2/Bax and 
      significantly decreasing cleaved caspase-3 expression. In addition, apelin-13 
      significantly inhibited excessive autophagy by regulating the expression of LC3B, 
      p62, and Beclin1. Furthermore, the expression of Bcl-2 and the 
      phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) 
      pathway was markedly increased. Both LY294002 (20 muM) and rapamycin (500 nM), 
      which are inhibitors of the PI3K/Akt/mTOR pathway, significantly attenuated the 
      inhibition of autophagy and apoptosis caused by apelin-13. In conclusion, the 
      findings of the present study suggest that Bcl-2 upregulation and mTOR signaling 
      pathway activation lead to the inhibition of apoptosis and excessive autophagy. 
      These effects are involved in apelin-13-induced neuroprotection against cerebral 
      ischemia/reperfusion injury, both in vivo and in vitro. The study was approved by 
      the Animal Ethical and Welfare Committee of Jining Medical University, China 
      (approval No. 2018-JS-001) in February 2018.
FAU - Shao, Zi-Qi
AU  - Shao ZQ
AD  - Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, 
      China.
FAU - Dou, Shan-Shan
AU  - Dou SS
AD  - Neurobiology Institute, Jining Medical University, Jining, Shandong Province, 
      China.
FAU - Zhu, Jun-Ge
AU  - Zhu JG
AD  - Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, 
      China.
FAU - Wang, Hui-Qing
AU  - Wang HQ
AD  - Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, 
      China.
FAU - Wang, Chun-Mei
AU  - Wang CM
AD  - Neurobiology Institute, Jining Medical University, Jining, Shandong Province, 
      China.
FAU - Cheng, Bao-Hua
AU  - Cheng BH
AD  - Neurobiology Institute, Jining Medical University, Jining, Shandong Province, 
      China.
FAU - Bai, Bo
AU  - Bai B
AD  - Neurobiology Institute, Jining Medical University, Jining, Shandong Province, 
      China.
LA  - eng
PT  - Journal Article
PL  - India
TA  - Neural Regen Res
JT  - Neural regeneration research
JID - 101316351
PMC - PMC8224111
OTO - NOTNLM
OT  - apoptosis
OT  - autophagy
OT  - brain
OT  - brain injury
OT  - central nervous system
OT  - factor
OT  - neuroprotection
OT  - pathways
OT  - regeneration
COIS- None
EDAT- 2020/12/04 06:00
MHDA- 2020/12/04 06:01
PMCR- 2020/11/27
CRDT- 2020/12/03 08:35
PHST- 2020/12/03 08:35 [entrez]
PHST- 2020/12/04 06:00 [pubmed]
PHST- 2020/12/04 06:01 [medline]
PHST- 2020/11/27 00:00 [pmc-release]
AID - NeuralRegenRes_2021_16_6_1044_300725 [pii]
AID - NRR-16-1044 [pii]
AID - 10.4103/1673-5374.300725 [doi]
PST - ppublish
SO  - Neural Regen Res. 2021 Jun;16(6):1044-1051. doi: 10.4103/1673-5374.300725.