title: CART attenuates endoplasmic reticulum stress response induced by cerebral ischemia and reperfusion through upregulating BDNF synthesis and secretion.
abstract: Cocaine and amphetamine regulated transcript (CART), a neuropeptide, has shown strong neuroprotective effects against cerebral ischemia and reperfusion (I/R) injury in vivo and in vitro. Here, we report a new effect of CART on ER stress which is induced by cerebral I/R in a rat model of middle cerebral artery occlusion (MCAO) or by oxygen and glucose deprivation (OGD) in cultured cortical neurons, as well as a new functionality of BDNF in the neuroprotection by CART against the ER stress in cerebral I/R. The results showed that CART was effective in reducing the neuronal apoptosis and expression of ER stress markers (GRP78, CHOP and cleaved caspase12), and increasing the BDNF expression in I/R injury rat cortex both in vivo and in vitro. In addition, the effects of CART on ischemia-induced neuronal apoptosis and ER stress were suppressed by tyrosine receptor kinase B (TrkB) IgG, whereas the effects of CART on BDNF transcription, synthesis and secretion were abolished by CREB siRNA. This work suggests that CART is functional in inhibiting the cerebral I/R-induced ER stress and neuronal apoptosis by facilitating the transcription, synthesis and secretion of BDNF in a CREB-dependent way.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Qiu
authors.forename: Shengdi
authors.initials: S
authors.lastname: Hu
authors.forename: Libing
authors.initials: L
authors.lastname: Liu
authors.forename: Man
authors.initials: M
authors.lastname: Chen
authors.forename: Lai
authors.initials: L
authors.lastname: Wang
authors.forename: Xianwei
authors.initials: X
authors.lastname: Zeng
authors.forename: Shigong
authors.initials: S
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001483:Base Sequence; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D017931:DNA Primers; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013312:Stress, Physiological; D015854:Up-Regulation; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
keywords: BDNF; CART; CATT/EBP homologous protein; CHOP; CREB; Cerebral ischemia; ER; Endoplasmic reticulum stress; GRP78; I/R; MCAO; Neuron; OGD; TrkB; brain derived neurotrophic factor; cAMP-response element binding protein; cocaine and amphetamine regulated transcript; eIF2α; endoplasmic reticulum; eukaryotic initiation factor 2α; glucose regulated protein 78; ischemia and reperfusion; middle cerebral artery occlusion; oxygen and glucose deprivation; tyrosine receptor kinase B