RTN1-C is involved in high glucose-aggravated neuronal cell subjected to oxygen-glucose deprivation and reoxygenation injury via endoplasmic reticulum stress.

Authors:
Jun Ling
Jun Ling
MOE Key Laboratory of Macromolecular Synthesis and Functionalization
United States
Jiqian Zhang
Jiqian Zhang
Anhui Normal University
China
Jian DU
Jian DU
the Second Affiliated Hospital of Dalian Medical University
China
Lijian Chen
Lijian Chen
College of Chemistry and Material Science
China

Brain Res Bull 2019 Apr 16;149:129-136. Epub 2019 Apr 16.

Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. Electronic address:

Background: Patients suffering from diabetes mellitus experience poor outcomes after ischemic stroke. RTN1-C, ER-associated proteins localized in endoplasmic reticulum (ER) membrane, plays an important role in ER stress-induced apoptosis and regulates cellular susceptibility to different apoptosis pathways. Overexpression of RTN1-C can aggravate cerebral ischemia/reperfusion injury (IRI). ER stress plays a crucial role in hyperglycemia-aggravated cerebral IRI. In this study, we aimed to investigate the role of RTN1-C in high glucose-aggravated OGD/R-induced cell damage.

Materials And Methods: N2a cells and primary neuronal cells were cultured in normal glucose or high glucose conditions. We used a model of oxygen-glucose deprivation followed by reoxygenation (OGD/R). RTN1-C shRNA was used to knock down RTN1-C. The chemical chaperone 4-phenylbutyric acid (4-PBA) is a low molecular weight fatty acid that has the ability to stabilize mutant proteins and facilitate their folding, was used to inhibited ER stress. Cell viability and apoptosis were measured by CCK-8 and flow cytometry assays. The contents of ER stress-associated proteins, such as GRP78, cleaved caspase-12, CHOP and cleaved caspase-3, were detected by western blot.

Results: High glucose significantly decreased cell viability and increased cell apoptosis in OGD/R-treated neuronal cells. The contents of GRP78, cleaved caspase-12, CHOP and cleaved caspase-3 under high glucose conditions were higher than those under normal glucose conditions after OGD/R. Importantly, inhibition of ER stress by 4-PBA alleviated the high glucose-aggravated OGD/R-induced cell damage. Here, we demonstrated that high glucose increases RTN1-C expression in OGD/R-treated cells. More importantly, knockdown of RTN1-C expression dramatically reversed the high glucose-aggravated change in cell viability and apoptosis and relieved ER stress in OGD/R-treated cells.

Conclusions: High glucose significantly increases RTN1-C expression in OGD/R-treated cells. RTN1-C affects high glucose-treated OGD/R cells by exacerbating ER stress.

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http://dx.doi.org/10.1016/j.brainresbull.2019.04.010DOI Listing
April 2019
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