title: Trehalose Inhibits Protein Aggregation Caused by Transient Ischemic Insults Through Preservation of Proteasome Activity, Not via Induction of Autophagy.
abstract: Protein aggregation has been proved to be a pathological basis accounting for neuronal death caused by either transient global ischemia or oxygen glucose deprivation (OGD), and inhibition of protein aggregation is emerging as a potential strategy of preventing brain damage. Trehalose was found to inhibit protein aggregation caused by neurodegenerative diseases via induction of autophagy, whereas its effect is still elusive on ischemia-induced protein aggregation. In this study, we investigated this issue by using rat model of transient global ischemia and SH-SY5Y model of OGD. We found that pretreatment with trehalose inhibited transient global ischemia-induced neuronal death in the hippocampus CA1 neurons and OGD-induced death in SH-SY5Y cells, which was associated with inhibition of the formation of ubiquitin-labeled protein aggregates and preservation of proteasome activity. In vitro study showed that the protection of trehalose against OGD-induced cell death and protein aggregation in SH-SY5Y cells was reversed when proteasome activity was inhibited by MG-132. Further studies revealed that trehalose prevented OGD-induced reduction of proteasome activity via suppression of both oxidative stress and endoplasmic reticulum stress. Particularly, our results showed that trehalose inhibited OGD-induced autophagy. Therefore, we demonstrated that proteasome dysfunction contributed to protein aggregation caused by ischemic insults and trehalose prevented protein aggregation via preservation of proteasome activity, not via induction of autophagy.
authors: Department of Radiology, First Hospital of Jilin University, Changchun, 130021, China.|Department of Neurosurgery, First Hospital of Jilin University, Changchun, 130021, People's Republic of China.
authors: Ye
authors: Y
authors: Li
authors: Department of Neurosurgery, First Hospital of Jilin University, Changchun, 130021, People's Republic of China.
authors: Yinan
authors: Y
authors: Luo
authors: Department of Neurology, First Hospital of Jilin University, Changchun, 130021, China.|Research Center of Neuroscience, First Hospital of Jilin University, Changchun, 130021, China.
authors: Tianfei
authors: T
authors: Luo
authors: Department of Neurosurgery, First Hospital of Jilin University, Changchun, 130021, People's Republic of China.
authors: Bin
authors: B
authors: Lu
authors: Department of Neurosurgery, First Hospital of Jilin University, Changchun, 130021, People's Republic of China.
authors: Chen
authors: C
authors: Wang
authors: Department of Emergent Medicine, People's Hospital of Jilin Province, Changchun, 130021, China.
authors: Yanhong
authors: Y
authors: Zhang
authors: Department of Anesthesiology, First Hospital of Jilin University, Changchun, 130021, China.
authors: Meihua
authors: M
authors: Piao
authors: Department of Anesthesiology, First Hospital of Jilin University, Changchun, 130021, China.
authors: Chunsheng
authors: C
authors: Feng
authors: Department of Neurosurgery, First Hospital of Jilin University, Changchun, 130021, People's Republic of China. gepf@jlu.edu.cn.|Research Center of Neuroscience, First Hospital of Jilin University, Changchun, 130021, China. gepf@jlu.edu.cn.
authors: Pengfei
authors: P
authors: Ge
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D066263:Protein Aggregation, Pathological / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014199:Trehalose / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D014199:Trehalose; D046988:Proteasome Endopeptidase Complex
keywords: Autophagy; Endoplasmic reticulum stress; Oxidative stress; Proteasome; Protein aggregation; Transient global ischemia; Trehalose