Thymosin β4 prevents oxygen-glucose deprivation/reperfusion-induced injury in rat cortical neurons
Zhongsheng Zhang, Shuangfeng Liu, Sichun HuangDepartment of Neurology, The 6th Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan 511518, People’s Republic of ChinaCorrespondence: Zhongsheng ZhangDepartment of Neurology, The 6th Affiliated H...
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Dove Medical Press
2019
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oai:doaj.org-article:327f2d8c2e5246a9a4ac038b6d5278152021-12-02T07:56:47ZThymosin β4 prevents oxygen-glucose deprivation/reperfusion-induced injury in rat cortical neurons1178-2021https://doaj.org/article/327f2d8c2e5246a9a4ac038b6d5278152019-08-01T00:00:00Zhttps://www.dovepress.com/thymosin-beta4-prevents-oxygen-glucose-deprivationreperfusion-induced--peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Zhongsheng Zhang, Shuangfeng Liu, Sichun HuangDepartment of Neurology, The 6th Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan 511518, People’s Republic of ChinaCorrespondence: Zhongsheng ZhangDepartment of Neurology, The 6th Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan 511518, People’s Republic of ChinaTel +86 135 3952 3445Email zzsllokyy@163.comPurpose: This study investigated whether thymosin (T) β4 protects against oxygen-glucose deprivation/reperfusion (OGD/R) injury in rat cortical neurons, as well as the underlying mechanisms.Methods: Primary rat cortical neurons were transfected with Tβ4 overexpression plasmid; the transfection efficiency was confirmed by detecting Tβ4 expression by fluorescence quantitative PCR and Western blotting. The OGD/R model was established and apoptotic cells were quantified by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling. Structural changes in the endoplasmic reticulum were visualized by transmission electron microscopy. The expression levels of 78-kDa glucose-regulated protein (GRP) 78, C/EBP-homologous protein (CHOP), B-cell lymphoma (Bcl)-2, and Bcl-2-associated X protein (Bax) were determined by Western blotting. The effect of Tβ4 on OGD/R injury was evaluated by adding exogenous Tβ4 to neuronal cultures.Results: Cortical neurons were identified by the expression of neuron-specific enolase. In OGD/R cells, the rate of apoptosis was increased and GRP78, CHOP, and Bax were upregulated whereas Bcl-2 was downregulated relative to the control group. These effects were reversed by Tβ4 overexpression. Endoplasmic reticulum (ER) stress was observed in the OGD/R group, but this was abolished in neurons overexpressing Tβ4. The protective effect of Tβ4 against OGD/R injury was also demonstrated in cells treated with exogenous Tβ4 (10 ng/mL), which blocked OGD/R-induced apoptosis by inhibiting ER stress-related and pro-apoptotic protein expression.Conclusion: Tβ4 prevents OGD/R-induced ER stress-dependent apoptosis in cortical neurons, and is a potential treatment for cerebral ischemia-reperfusion injury.Keywords: Tβ4, cortical neuron culture, OGD/R, endoplasmic reticulum stressZhang ZLiu SHuang SDove Medical PressarticleTβ4cortical neuron cultureOGD/Rendoplasmic reticulum stress.Neurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 15, Pp 2385-2393 (2019) |
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DOAJ |
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EN |
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Tβ4 cortical neuron culture OGD/R endoplasmic reticulum stress. Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 |
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Tβ4 cortical neuron culture OGD/R endoplasmic reticulum stress. Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Zhang Z Liu S Huang S Thymosin β4 prevents oxygen-glucose deprivation/reperfusion-induced injury in rat cortical neurons |
| description |
Zhongsheng Zhang, Shuangfeng Liu, Sichun HuangDepartment of Neurology, The 6th Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan 511518, People’s Republic of ChinaCorrespondence: Zhongsheng ZhangDepartment of Neurology, The 6th Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan 511518, People’s Republic of ChinaTel +86 135 3952 3445Email zzsllokyy@163.comPurpose: This study investigated whether thymosin (T) β4 protects against oxygen-glucose deprivation/reperfusion (OGD/R) injury in rat cortical neurons, as well as the underlying mechanisms.Methods: Primary rat cortical neurons were transfected with Tβ4 overexpression plasmid; the transfection efficiency was confirmed by detecting Tβ4 expression by fluorescence quantitative PCR and Western blotting. The OGD/R model was established and apoptotic cells were quantified by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling. Structural changes in the endoplasmic reticulum were visualized by transmission electron microscopy. The expression levels of 78-kDa glucose-regulated protein (GRP) 78, C/EBP-homologous protein (CHOP), B-cell lymphoma (Bcl)-2, and Bcl-2-associated X protein (Bax) were determined by Western blotting. The effect of Tβ4 on OGD/R injury was evaluated by adding exogenous Tβ4 to neuronal cultures.Results: Cortical neurons were identified by the expression of neuron-specific enolase. In OGD/R cells, the rate of apoptosis was increased and GRP78, CHOP, and Bax were upregulated whereas Bcl-2 was downregulated relative to the control group. These effects were reversed by Tβ4 overexpression. Endoplasmic reticulum (ER) stress was observed in the OGD/R group, but this was abolished in neurons overexpressing Tβ4. The protective effect of Tβ4 against OGD/R injury was also demonstrated in cells treated with exogenous Tβ4 (10 ng/mL), which blocked OGD/R-induced apoptosis by inhibiting ER stress-related and pro-apoptotic protein expression.Conclusion: Tβ4 prevents OGD/R-induced ER stress-dependent apoptosis in cortical neurons, and is a potential treatment for cerebral ischemia-reperfusion injury.Keywords: Tβ4, cortical neuron culture, OGD/R, endoplasmic reticulum stress |
| format |
article |
| author |
Zhang Z Liu S Huang S |
| author_facet |
Zhang Z Liu S Huang S |
| author_sort |
Zhang Z |
| title |
Thymosin β4 prevents oxygen-glucose deprivation/reperfusion-induced injury in rat cortical neurons |
| title_short |
Thymosin β4 prevents oxygen-glucose deprivation/reperfusion-induced injury in rat cortical neurons |
| title_full |
Thymosin β4 prevents oxygen-glucose deprivation/reperfusion-induced injury in rat cortical neurons |
| title_fullStr |
Thymosin β4 prevents oxygen-glucose deprivation/reperfusion-induced injury in rat cortical neurons |
| title_full_unstemmed |
Thymosin β4 prevents oxygen-glucose deprivation/reperfusion-induced injury in rat cortical neurons |
| title_sort |
thymosin β4 prevents oxygen-glucose deprivation/reperfusion-induced injury in rat cortical neurons |
| publisher |
Dove Medical Press |
| publishDate |
2019 |
| url |
https://doaj.org/article/327f2d8c2e5246a9a4ac038b6d527815 |
| work_keys_str_mv |
AT zhangz thymosinbeta4preventsoxygenglucosedeprivationreperfusioninducedinjuryinratcorticalneurons AT lius thymosinbeta4preventsoxygenglucosedeprivationreperfusioninducedinjuryinratcorticalneurons AT huangs thymosinbeta4preventsoxygenglucosedeprivationreperfusioninducedinjuryinratcorticalneurons |
| _version_ |
1718399092950827008 |