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Apoptosis

pp 1–18 | Cite as

BDNF-mediated mitophagy alleviates high-glucose-induced brain microvascular endothelial cell injury

  • Hong JinEmail author
  • Yi Zhu
  • Yiping Li
  • Xiuyu Ding
  • Wenqi Ma
  • Xiqiong Han
  • Bilei Wang
Article

Abstract

Endothelial cell dysfunction and diabetic vascular complications are intrinsically linked. Although BDNF plays a protective role in cerebral microvascular complications caused by diabetes, the mechanisms of this activity are not fully clear. In this study, we investigated the role of BDNF in the hyperglycemic injury of BMECs and its associated intracellular signal transduction pathways. BMECs were treated with 33 mM glucose to imitate the endothelium under hyperglycemic conditions. The high-glucose treatment caused cell dysfunction, as evaluated by oxidative stress and cell apoptosis, which could be alleviated by BDNF. In addition, BDNF preserved mitochondrial function as assessed by mPTP opening, mitochondrial membrane potential, calcium content, and mitochondrial biogenesis markers. Western blot analysis of LC3-II, p62, and TOMM20 and the detection of mRFP-GFP-LC3 adenovirus for autophagy flux revealed that BDNF enhanced autophagy flux. Furthermore, BDNF activated mitophagy, which was confirmed by the observed colocalization of LC3-II with BNIP3 and from transmission electron microscopy observations. The HIF-1α/BNIP3 signaling pathway was associated with BDNF/TrkB-induced mitophagy. In addition, BDNF-induced mitophagy played a protective role against BMEC damage under hyperglycemia. Thus, the results of this study suggest that BDNF/TrkB/HIF-1α/BNIP3-mediated mitophagy protects BMECs from hyperglycemia.

Keywords

BDNF BMECs Hyperglycemia Mitochondrial function Mitophagy 

Abbreviations

BDNF

Brain-derived neurotrophic factor

BMECs

Brain microvascular endothelial cells

mPTP

Mitochondrial permeability transition pore

LC3-II

Microtubule-associated protein 1 light chain 3B

p62

SQSTM1

TOMM20

Translocase of outer mitochondrial membrane 20

HIF-1α

Hypoxia-inducible factor-1α

TrkB

Tropomyosin receptor or kinase B

BNIP3

BCL2/adenovirus E1B 19 kDa protein-interacting protein 3

Notes

Acknowledgements

This work was supported by the Fundamental Research Funds for the Central Universities and Postgraduate Research & Practice Innovation Program of Jiangsu Province (No. KYCX17_0174) and the Jiangsu Provincial Health and Wellness Committee Research Project (No. H2018001).

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest.

Supplementary material

10495_2019_1535_MOESM1_ESM.docx (888 kb)
Supplementary material 1 (DOCX 888 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Hong Jin
    • 1
    Email author
  • Yi Zhu
    • 1
  • Yiping Li
    • 1
  • Xiuyu Ding
    • 2
  • Wenqi Ma
    • 1
  • Xiqiong Han
    • 1
  • Bilei Wang
    • 1
  1. 1.Department of Cardiology, School of Medicine, Zhongda HospitalSoutheast UniversityNanjingPeople’s Republic of China
  2. 2.Nanjing Ninghai Middle SchoolNanjingPeople’s Republic of China

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