Pro-BDNF Contributes to HypoxiaReoxygenation Injury in Myocardial Microvascular Endothelial Cells: Roles of Receptors p75NTR and Sortilin and Activation of JNK and Caspase 3
Joint Authors
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-06-26
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
The aim of this study was to identify the role of the precursor of the brain-derived neurotrophic factor (pro-BDNF) in myocardial hypoxia/reoxygenation injury (H/R) and to address the underlying mechanisms.
For this purpose, myocardial microvascular endothelial cells (MMECs) exposed to a high concentration of glucose (30 mM) for 48 h were subjected to 4 h of hypoxia followed by 2 h of reoxygenation.
Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining and flow-cytometric analysis were performed to detect apoptosis.
Cell scratch and capillary-like-structure formation assays were employed to evaluate cell function.
The levels of apoptosis-related proteins were evaluated by Western blotting and immunofluorescence assays.
Our results showed that H/R resulted in MMEC injury, as indicated by significant increases in TUNEL-positive cell numbers and a reduction in MMEC migration and in capillary-like-structure formation coupled with increased pro-BDNF protein expression.
In addition, overexpression of pro-BDNF in MMECs via a viral vector led to increased pro-BDNF expression, and this upregulation induced apoptosis.
Mechanistic experiments revealed that H/R did not influence BDNF, JNK, and caspase 3 expression, but upregulated pro-BDNF, p75NTR, sortilin, phospho-JNK, and cleaved caspase 3 protein levels.
In contrast, neutralization of endogenous pro-BDNF with an antibody significantly attenuated H/R-induced upregulation of pro-BDNF, p75NTR, sortilin, p-JNK, and cleaved caspase 3 protein levels, indicating that p75NTR-sortilin signaling and activation of JNK and caspase 3 may be involved in these effects.
In conclusion, H/R-induced injury may be mediated by pro-BDNF, at least in part through the regulation of p75NTR-sortilin signaling and activation of JNK and caspase 3.
American Psychological Association (APA)
Yu, Fei& Liu, Yuezhu& Xu, Junmei. 2018. Pro-BDNF Contributes to HypoxiaReoxygenation Injury in Myocardial Microvascular Endothelial Cells: Roles of Receptors p75NTR and Sortilin and Activation of JNK and Caspase 3. Oxidative Medicine and Cellular Longevity،Vol. 2018, no. 2018, pp.1-11.
https://search.emarefa.net/detail/BIM-1211152
Modern Language Association (MLA)
Yu, Fei…[et al.]. Pro-BDNF Contributes to HypoxiaReoxygenation Injury in Myocardial Microvascular Endothelial Cells: Roles of Receptors p75NTR and Sortilin and Activation of JNK and Caspase 3. Oxidative Medicine and Cellular Longevity No. 2018 (2018), pp.1-11.
https://search.emarefa.net/detail/BIM-1211152
American Medical Association (AMA)
Yu, Fei& Liu, Yuezhu& Xu, Junmei. Pro-BDNF Contributes to HypoxiaReoxygenation Injury in Myocardial Microvascular Endothelial Cells: Roles of Receptors p75NTR and Sortilin and Activation of JNK and Caspase 3. Oxidative Medicine and Cellular Longevity. 2018. Vol. 2018, no. 2018, pp.1-11.
https://search.emarefa.net/detail/BIM-1211152
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1211152