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Transduced Tat-PRAS40 prevents dopaminergic neuronal cell death through ROS inhibition and interaction with 14-3-sigma protein

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Abstract
Proline rich Akt substrate (PRAS40) is a component of mammalian target of rapamycin complex 1 (mTORC1) and activated mTORC1 plays important roles for cellular survival in response to oxidative stress. However, the roles of PRAS40 in dopaminergic neuronal cell death have not yet been examined. Here, we examined the roles of Tat-PRAS40 in MPP+- and MPTP-induced dopaminergic neuronal cell death. Our results showed that Tat-PRAS40 effectively transduced into SH-SY5Y cells and inhibited DNA damage, ROS generation, and apoptotic signaling in MPP+-induced SH-SY5Y cells. Further, these protective mechanisms of Tat-PRAS40 protein display through phosphorylation of Tat-PRAS40, Akt and direct interaction with 14-3-3 sigma protein, but not via the mTOR-dependent signaling pathway. In a Parkinson's disease animal model, Tat-PRAS40 transduced into dopaminergic neurons in mouse brain and significantly protected against dopaminergic cell death by phosphorylation of Tat-PRAS40, Akt and interaction with 14-3-3 sigma protein. In this study, we demonstrated for the first time that Tat-PRAS40 directly protects against dopaminergic neuronal cell death. These results indicate that Tat-PRAS40 may provide a useful therapeutic agent against oxidative stress-induced dopaminergic neuronal cell death, which causes diseases such as PD.
Author(s)
음원식김대원여은지여현지최연주차현주박진서한규형김덕수유연희조성우권오신조용준신민재최수영
Issued Date
2021
Type
Article
Keyword
AnalysisBiochemistryCell deathMedical collegesNeurons
DOI
10.1016/j.freeradbiomed.2021.06.026
URI
https://oak.ulsan.ac.kr/handle/2021.oak/8014
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_gale_infotracacademiconefile_A670936824&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Transduced%20Tat-PRAS40%20prevents%20dopaminergic%20neuronal%20cell%20death%20through%20ROS%20inhibition%20and%20interaction%20with%2014-3-sigma%20protein&offset=0&pcAvailability=true
Publisher
FREE RADICAL BIOLOGY AND MEDICINE
Location
네덜란드
Language
영어
ISSN
0891-5849
Citation Volume
172
Citation Number
.
Citation Start Page
418
Citation End Page
429
Appears in Collections:
Medicine > Medicine
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