Open AccessOrexin-A alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress-mediated apoptosis
Author(s) -
Dandan Xu,
Tingting Kong,
Baohua Cheng,
Rumin Zhang,
Chunqing Yang,
Jing Chen,
Chunmei Wang
Publication year - 2021
Publication title -
molecular medicine reports
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2021.11905
Subject(s) - neuroprotection , apoptosis , tunel assay , reperfusion injury , ischemia , chop , endoplasmic reticulum , biology , blot , pharmacology , caspase 3 , microbiology and biotechnology , endocrinology , medicine , programmed cell death , biochemistry , gene
Orexin‑A (OXA) protects neurons against cerebral ischemia‑reperfusion injury (CIRI). Endoplasmic reticulum stress (ERS) induces apoptosis after CIRI by activating caspase‑12 and the CHOP pathway. The present study aimed to determine whether OXA mitigates CIRI by inhibiting ERS‑induced neuronal apoptosis. A model of CIRI was established, in which rats were subjected to middle cerebral artery occlusion with ischemic intervention for 2 h, followed by reperfusion for 24 h. Neurological deficit examination and 2,3,5‑triphenyltetrazolium chloride staining were performed to assess the level of CIRI and neuroprotection by OXA. Expression levels of ERS‑related proteins and cleaved caspase‑3 were measured via western blotting, while the rate of neuronal apoptosis in the cortex was determined using a TUNEL assay. OXA treatment decreased the infarct volume of rats after CIRI and attenuated neuron apoptosis. Furthermore, administration of OXA decreased the expression levels of GRP78, phosphorylated (p)‑PERK, p‑eukaryotic initiation factor‑2α, p‑inositol requiring enzyme 1α, p‑JNK, cleaved caspase‑12, CHOP and cleaved caspase‑3, all of which were induced by CIRI. Collectively, these findings suggested that OXA attenuated CIRI by inhibiting ERS‑mediated apoptosis, thus clarifying the mechanism underlying its neuroprotective effect and providing a novel therapeutic direction for the treatment of CIRI.