Propofol Protects Hippocampal Neurons from Hypoxia-Reoxygenation Injury by Decreasing Calcineurin-Induced Calcium Overload and Activating YAP Signaling
Joint Authors
Cai, Hui
Li, Xiaojun
Yao, Li
Liang, Qianlei
Qu, Hangyin
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-06-26
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Objectives.
Propofol is a popular anesthetic drug that is neuroprotective.
However, the mechanisms of propofol for hippocampal neuroprotection remain elusive.
This study is aimed at investigating the neuroprotective effect and mechanism of propofol in hippocampal neurons exposed to ischemia-reperfusion (I/R) injury.
Methods.
Hypoxia-reoxygenated (H/R) HT-22 cells were used to mimic I/R injury of the hippocampus in vitro.
An MTT assay was used to determine cell viability.
Cell apoptosis was detected by a TUNEL assay and a flow cytometry cell apoptosis assay.
Expression levels of proteins were measured by Western blotting.
Intracellular calcium was assessed by Fura-2/AM staining.
Flow cytometry was used to determine the mitochondrial membrane potential (MMP).
Coimmunoprecipitation was used to evaluate the stability of the FKBP-RyR complex.
Calcineurin enzymatic activity was measured with a colorimetric method.
YAP nuclear translocation was tested by immunofluorescence staining.
Results.
H/R induced HT-22 cell viability depression, and apoptosis was reversed by propofol treatment.
Propofol could alleviate H/R-induced intracellular calcium accumulation and MMP loss by inhibiting calcineurin activity and FKBP12.6-RyR disassociation in a concentration-dependent manner.
In addition, YAP expression was crucial for propofol to protect HT-22 cell apoptosis from H/R injury.
Propofol could activate YAP through dephosphorylation.
Activated YAP stimulated the transcription of the Bcl2 gene, which promotes cellular survival.
Our data also demonstrated that propofol activated YAP through the RhoA-Lats1 pathway without large G proteins or MST involvement.
In addition, we showed that there was no interaction between calcineurin signaling and YAP activation in HT-22 cells.
Conclusions.
Propofol protected hippocampal neurons from I/R injury through two independent signaling pathways, including the calcineurin/FKBP12.6-RyR/calcium overload pathway and the RhoA/Lats1/YAP/Bcl-2 pathway.
American Psychological Association (APA)
Li, Xiaojun& Yao, Li& Liang, Qianlei& Qu, Hangyin& Cai, Hui. 2018. Propofol Protects Hippocampal Neurons from Hypoxia-Reoxygenation Injury by Decreasing Calcineurin-Induced Calcium Overload and Activating YAP Signaling. Oxidative Medicine and Cellular Longevity،Vol. 2018, no. 2018, pp.1-12.
https://search.emarefa.net/detail/BIM-1210904
Modern Language Association (MLA)
Li, Xiaojun…[et al.]. Propofol Protects Hippocampal Neurons from Hypoxia-Reoxygenation Injury by Decreasing Calcineurin-Induced Calcium Overload and Activating YAP Signaling. Oxidative Medicine and Cellular Longevity No. 2018 (2018), pp.1-12.
https://search.emarefa.net/detail/BIM-1210904
American Medical Association (AMA)
Li, Xiaojun& Yao, Li& Liang, Qianlei& Qu, Hangyin& Cai, Hui. Propofol Protects Hippocampal Neurons from Hypoxia-Reoxygenation Injury by Decreasing Calcineurin-Induced Calcium Overload and Activating YAP Signaling. Oxidative Medicine and Cellular Longevity. 2018. Vol. 2018, no. 2018, pp.1-12.
https://search.emarefa.net/detail/BIM-1210904
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1210904