Adiponectin Protects Against Cerebral Ischemic Injury Through AdipoR1/AMPK Pathways
Excitotoxicity induced by excessive N-methyl-D-aspartate (NMDA) receptor activation underlies the pathology of ischemic injury. Adiponectin (APN) is an adipocyte-derived protein hormone that modulates a number of metabolic processes. APN exerts a wide range of biological functions in the central ner...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.00597/full |
| _version_ | 1819130251388649472 |
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| author | Bin Liu Jing Liu Jiangong Wang Fengjiao Sun Shujun Jiang Fengai Hu Dan Wang Dunjiang Liu Cuilan Liu Haijing Yan |
| author_facet | Bin Liu Jing Liu Jiangong Wang Fengjiao Sun Shujun Jiang Fengai Hu Dan Wang Dunjiang Liu Cuilan Liu Haijing Yan |
| author_sort | Bin Liu |
| collection | DOAJ |
| description | Excitotoxicity induced by excessive N-methyl-D-aspartate (NMDA) receptor activation underlies the pathology of ischemic injury. Adiponectin (APN) is an adipocyte-derived protein hormone that modulates a number of metabolic processes. APN exerts a wide range of biological functions in the central nervous system. However, the role of APN and its receptors in cerebral ischemia/reperfusion (I/R)-induced injury and the related mechanisms remain to be clarified. Here, we found that APN and APN receptor agonist AdipoRon (APR) were protective against excitotoxicity induced by oxygen and glucose deprivation/reperfusion (OGD/R) and NMDA in primary neurons. Adiponectin receptor 1 (AdipoR1) knockdown reversed the protection conferred by either APN or APR. Moreover, the protective effects offered by both APN and APR were compromised by compound C, an inhibitor of amp-activated protein kinase (AMPK) phosphorylation. Both APN and APR protected the dissipation of the ΔΨm caused by OGD/R. They also up-regulated the PGC-1α expression, which was reversed by compound C. Furthermore, both APN and APR ameliorated but APN knockout aggravated the infarct volume and neurological deficient induced by transient middle cerebral artery occlusion (tMCAO) in vivo. Taken together, these findings show that APN and APR protect against ischemic injury in vitro and in vivo. The protective mechanism is mainly related to AdipoR1-dependent AMPK phosphorylation and PGC-1α up-regulation. |
| first_indexed | 2024-12-22T08:56:38Z |
| format | Article |
| id | doaj.art-e0785f14b2844f21a13db52e0b9267b7 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-22T08:56:38Z |
| publishDate | 2019-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-e0785f14b2844f21a13db52e0b9267b72022-12-21T18:31:49ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-05-011010.3389/fphar.2019.00597442581Adiponectin Protects Against Cerebral Ischemic Injury Through AdipoR1/AMPK PathwaysBin LiuJing LiuJiangong WangFengjiao SunShujun JiangFengai HuDan WangDunjiang LiuCuilan LiuHaijing YanExcitotoxicity induced by excessive N-methyl-D-aspartate (NMDA) receptor activation underlies the pathology of ischemic injury. Adiponectin (APN) is an adipocyte-derived protein hormone that modulates a number of metabolic processes. APN exerts a wide range of biological functions in the central nervous system. However, the role of APN and its receptors in cerebral ischemia/reperfusion (I/R)-induced injury and the related mechanisms remain to be clarified. Here, we found that APN and APN receptor agonist AdipoRon (APR) were protective against excitotoxicity induced by oxygen and glucose deprivation/reperfusion (OGD/R) and NMDA in primary neurons. Adiponectin receptor 1 (AdipoR1) knockdown reversed the protection conferred by either APN or APR. Moreover, the protective effects offered by both APN and APR were compromised by compound C, an inhibitor of amp-activated protein kinase (AMPK) phosphorylation. Both APN and APR protected the dissipation of the ΔΨm caused by OGD/R. They also up-regulated the PGC-1α expression, which was reversed by compound C. Furthermore, both APN and APR ameliorated but APN knockout aggravated the infarct volume and neurological deficient induced by transient middle cerebral artery occlusion (tMCAO) in vivo. Taken together, these findings show that APN and APR protect against ischemic injury in vitro and in vivo. The protective mechanism is mainly related to AdipoR1-dependent AMPK phosphorylation and PGC-1α up-regulation.https://www.frontiersin.org/article/10.3389/fphar.2019.00597/fulladiponectinAdipoRonischemiaadiponectin receptor 1amp-activated protein kinasePGC-1α |
| spellingShingle | Bin Liu Jing Liu Jiangong Wang Fengjiao Sun Shujun Jiang Fengai Hu Dan Wang Dunjiang Liu Cuilan Liu Haijing Yan Adiponectin Protects Against Cerebral Ischemic Injury Through AdipoR1/AMPK Pathways Frontiers in Pharmacology adiponectin AdipoRon ischemia adiponectin receptor 1 amp-activated protein kinase PGC-1α |
| title | Adiponectin Protects Against Cerebral Ischemic Injury Through AdipoR1/AMPK Pathways |
| title_full | Adiponectin Protects Against Cerebral Ischemic Injury Through AdipoR1/AMPK Pathways |
| title_fullStr | Adiponectin Protects Against Cerebral Ischemic Injury Through AdipoR1/AMPK Pathways |
| title_full_unstemmed | Adiponectin Protects Against Cerebral Ischemic Injury Through AdipoR1/AMPK Pathways |
| title_short | Adiponectin Protects Against Cerebral Ischemic Injury Through AdipoR1/AMPK Pathways |
| title_sort | adiponectin protects against cerebral ischemic injury through adipor1 ampk pathways |
| topic | adiponectin AdipoRon ischemia adiponectin receptor 1 amp-activated protein kinase PGC-1α |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.00597/full |
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