Apelin-13 inhibits apoptosis and excessive autophagy in cerebral ischemia/reperfusion injury
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...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2021-01-01
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| Series: | Neural Regeneration Research |
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| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2021;volume=16;issue=6;spage=1044;epage=1051;aulast=Shao |
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| author | Zi-Qi Shao Shan-Shan Dou Jun-Ge Zhu Hui-Qing Wang Chun-Mei Wang Bao-Hua Cheng Bo Bai |
| author_facet | Zi-Qi Shao Shan-Shan Dou Jun-Ge Zhu Hui-Qing Wang Chun-Mei Wang Bao-Hua Cheng Bo Bai |
| author_sort | Zi-Qi Shao |
| collection | DOAJ |
| description | 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 μg/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% N2 and 5% CO2 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 μM) 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. |
| first_indexed | 2024-12-17T20:27:50Z |
| format | Article |
| id | doaj.art-78979e7c86b64b49bd1a7c10fd717c08 |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-12-17T20:27:50Z |
| publishDate | 2021-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-78979e7c86b64b49bd1a7c10fd717c082022-12-21T21:33:42ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742021-01-011661044105110.4103/1673-5374.300725Apelin-13 inhibits apoptosis and excessive autophagy in cerebral ischemia/reperfusion injuryZi-Qi ShaoShan-Shan DouJun-Ge ZhuHui-Qing WangChun-Mei WangBao-Hua ChengBo BaiApelin-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 μg/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% N2 and 5% CO2 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 μM) 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.http://www.nrronline.org/article.asp?issn=1673-5374;year=2021;volume=16;issue=6;spage=1044;epage=1051;aulast=Shaocentral nervous system; brain; brain injury; factor; pathways; apoptosis; autophagy; neuroprotection; regeneration |
| spellingShingle | Zi-Qi Shao Shan-Shan Dou Jun-Ge Zhu Hui-Qing Wang Chun-Mei Wang Bao-Hua Cheng Bo Bai Apelin-13 inhibits apoptosis and excessive autophagy in cerebral ischemia/reperfusion injury Neural Regeneration Research central nervous system; brain; brain injury; factor; pathways; apoptosis; autophagy; neuroprotection; regeneration |
| title | Apelin-13 inhibits apoptosis and excessive autophagy in cerebral ischemia/reperfusion injury |
| title_full | Apelin-13 inhibits apoptosis and excessive autophagy in cerebral ischemia/reperfusion injury |
| title_fullStr | Apelin-13 inhibits apoptosis and excessive autophagy in cerebral ischemia/reperfusion injury |
| title_full_unstemmed | Apelin-13 inhibits apoptosis and excessive autophagy in cerebral ischemia/reperfusion injury |
| title_short | Apelin-13 inhibits apoptosis and excessive autophagy in cerebral ischemia/reperfusion injury |
| title_sort | apelin 13 inhibits apoptosis and excessive autophagy in cerebral ischemia reperfusion injury |
| topic | central nervous system; brain; brain injury; factor; pathways; apoptosis; autophagy; neuroprotection; regeneration |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2021;volume=16;issue=6;spage=1044;epage=1051;aulast=Shao |
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