Nrdp1 is involved in hippocampus apoptosis in cardiopulmonary bypass-induced cognitive dysfunction via the regulation of ErbB3 protein levels

Zheng,Jie; Min,Su; Hu,Bin; Liu,Qin; Wan,Yunqiang

doi:10.3892/ijmm.2019.4080

Nrdp1 is involved in hippocampus apoptosis in cardiopulmonary bypass-induced cognitive dysfunction via the regulation of ErbB3 protein levels

Authors:
- Jie Zheng
- Su Min
- Bin Hu
- Qin Liu
- Yunqiang Wan
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Affiliations: Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Anesthesiology, Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University, Luzhou, Sichuan 640000, P.R. China, Department of Anesthesiology, The First Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
Published online on: January 28, 2019 https://doi.org/10.3892/ijmm.2019.4080
Pages: 1747-1757
Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The cardiopulmonary bypass (CPB) is an important risk factor for the development of postoperative cognitive dysfunction (POCD). The pathological mechanism of the neuro‑modulation receptor degradation protein ring finger protein 41 (Nrdp1) in CPB‑induced cognitive dysfunction remains unclear. In the present study, aged Sprague‑Dawley male rats and CPB treatment were selected to duplicate the POCD model. A hypoxia/reoxygeneration (H/R) model was established to evaluate the effect of Nrdp1 in vitro. Apoptosis in the hippocampus regions were measured using a terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labelling assay, the viability and apoptosis level of the cells were measured via an MTT assay and flow cytometry, respectively, and the expression levels of Nrdp1, erb‑b2 receptor tyrosine kinase 3 (ErbB3), phosphorylated‑protein kinase B (p‑AKT) and cleaved (c‑) caspase‑3 were detected using western blot analysis. Then, Nrdp1 was upregulated and downregulated in vitro and in vivo through lentivirus infection to further investigate the effect of Nrdp1 in the rats following CPB. The results revealed that Nrdp1 is associated with hippocampus neuronal apoptosis and POCD following CPB in rats. The overexpression of Nrdp1 altered the cognitive function of the rats which was inhibited by CPB, and additionally inhibited the viability and increased the apoptosis of primary hippocampus neuron cells under H/R treatment. Furthermore, knockdown of Nrdp1 promoted the viability of primary hippocampus neuron cells and decreased the apoptosis of cells under H/R treatment. Further study indicated that Nrdp1 regulates the protein expression of ErbB3, p‑AKT, cytochrome c, BCL2-associated X, apoptosis regulator, BCL2, apoptosis regulator and c‑caspase‑3. The results of the present study suggested that CPB may induce apoptosis in the hippocampus of aged rats. Nrdp1 serves an important role in regulating the apoptosis induced by CPB in vivo and in vitro through regulating ErbB3 and p‑AKT protein levels.

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