Skip to main content
SpringerLink
Log in

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

  • Published:
Apoptosis Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

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

References

  1. Schiel R, Stachow R, Hermann T et al (2018) Rehabilitation in Germany 2004–2016 A Multicenter Analysis Over a Period of 13 Years in Children and Adolescents with Diabetes Mellitus. Experimental and clinical endocrinology & diabetes: official journal, German Society of Endocrinology [and] German Diabetes Association

  2. Xu R, Yang R, Hu H, Xi Q, Wan H, Wu Y (2013) Diabetes alters the expression of partial vasoactivators in cerebral vascular disease susceptible regions of the diabetic rat. Diabetol Metab Syndr 5:63

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Cantu-Brito C, Mimenza-Alvarado A, Sanchez-Hernandez JJ (2010) Diabetes mellitus and aging as a risk factor for cerebral vascular disease: epidemiology, pathophysiology and prevention. Revista de investigacion clinica 62:333–342

    PubMed  Google Scholar 

  4. Ergul A, Abdelsaid M, Fouda AY, Fagan SC (2014) Cerebral neovascularization in diabetes: implications for stroke recovery and beyond. J Cereb Blood Flow Metab 34:553–563

    Article  PubMed  PubMed Central  Google Scholar 

  5. Li H, Gao A, Feng D et al (2014) Evaluation of the protective potential of brain microvascular endothelial cell autophagy on blood-brain barrier integrity during experimental cerebral ischemia-reperfusion injury. Transl Stroke Res 5:618–626

    Article  PubMed  Google Scholar 

  6. Guo S, Deng W, Xing C, Zhou Y, Ning M, Lo EH (2018) Effects of aging, hypertension and diabetes on the mouse brain and heart vasculomes. Neurobiol Dis. https://doi.org/10.1016/j.nbd.2018.07.021

    Article  PubMed  PubMed Central  Google Scholar 

  7. Guan G, Han H, Yang Y, Jin Y, Wang X, Liu X (2014) Neferine prevented hyperglycemia-induced endothelial cell apoptosis through suppressing ROS/Akt/NF-kappaB signal. Endocrine 47:764–771

    Article  CAS  PubMed  Google Scholar 

  8. Zhao Y, Huang S, Liu J et al (2018) Mitophagy contributes to the pathogenesis of inflammatory diseases. Inflammation 41(5):1590–1600

    Article  CAS  PubMed  Google Scholar 

  9. Di Rita A, D’Acunzo P, Simula L, Campello S, Strappazzon F, Cecconi F (2018) AMBRA1-mediated mitophagy counteracts oxidative stress and apoptosis induced by neurotoxicity in human neuroblastoma SH-SY5Y cells. Front Cell Neurosci 12:92

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lohitesh K, Saini H, Srivastava A, Mukherjee S, Roy A, Chowdhury R (2018) Autophagy inhibition potentiates SAHAmediated apoptosis in glioblastoma cells by accumulation of damaged mitochondria. Oncol Rep 39:2787–2796

    CAS  PubMed  Google Scholar 

  11. Chakrabarty S, Kabekkodu SP, Singh RP, Thangaraj K, Singh KK, Satyamoorthy K (2018) Mitochondria in health and disease. Mitochondrion 43:25–29

    Article  CAS  PubMed  Google Scholar 

  12. Abdelwahid E, Stulpinas A, Kalvelyte A (2017) Effective agents targeting the mitochondria and apoptosis to protect the heart. Curr Pharm Des 23:1153–1166

    Article  CAS  PubMed  Google Scholar 

  13. Thangaraj A, Periyasamy P (2018) HIV-1 TAT-mediated microglial activation: role of mitochondrial dysfunction and defective mitophagy. Autophagy 14(9):1596–1619.

    Article  CAS  Google Scholar 

  14. Lan R, Wu JT, Wu T et al (2018) Mitophagy is activated in brain damage induced by cerebral ischemia and reperfusion via the PINK1/Parkin/p62 signalling pathway. Brain Res Bull 142:63–77

    Article  CAS  Google Scholar 

  15. Marshall J, Zhou XZ, Chen G et al (2018) Antidepression action of BDNF requires and is mimicked by Galphai1/3 expression in the hippocampus. 115:e3549–e3558

  16. Eyileten C, Zaremba M, Janicki PK et al (2016) Serum brain-derived neurotrophic factor is related to platelet reactivity but not to genetic polymorphisms within BDNF encoding gene in patients with type 2 diabetes. Med Sci Monit 22:69–76

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Li B, Lang N, Cheng ZF (2016) Serum levels of brain-derived neurotrophic factor are associated with diabetes risk, complications, and obesity: a cohort study from chinese patients with type 2 diabetes. Mol Neurobiol 53:5492–5499

    Article  CAS  PubMed  Google Scholar 

  18. Jin H, Chen Y, Wang B et al (2018) Association between brain-derived neurotrophic factor and von Willebrand factor levels in patients with stable coronary artery disease. BMC Cardiovasc Disord 18:23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wood J, Tse MCL, Yang X et al (2018) BDNF mimetic alleviates body weight gain in obese mice by enhancing mitochondrial biogenesis in skeletal muscle. Metabolism 87:113–122

  20. Navaratna D, Guo SZ, Hayakawa K, Wang X, Gerhardinger C, Lo EH (2011) Decreased cerebrovascular brain-derived neurotrophic factor-mediated neuroprotection in the diabetic brain. Diabetes 60:1789–1796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Navaratna D, Fan X, Leung W et al (2013) Cerebrovascular degradation of TRKB by MMP9 in the diabetic brain. J Clin Invest 123:3373–3377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Huang C, Zhang Y, Kelly DJ et al (2016) Thioredoxin interacting protein (TXNIP) regulates tubular autophagy and mitophagy in diabetic nephropathy through the mTOR signaling pathway. Sci Rep 6:29196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Nakamura K, Martin KC, Jackson JK, Beppu K, Woo CW, Thiele CJ (2006) Brain-derived neurotrophic factor activation of TrkB induces vascular endothelial growth factor expression via hypoxia-inducible factor-1alpha in neuroblastoma cells. Cancer Res 66:4249–4255

    Article  CAS  PubMed  Google Scholar 

  24. Gao Y, Jing M, Ge R, Lang L (2016) Induction of hypoxia-inducible factor-1alpha by BDNF protects retinoblastoma cells against chemotherapy-induced apoptosis. Molecular cellular biochemistry 414:77–84

    Article  CAS  PubMed  Google Scholar 

  25. Feng CC, Lin CC, Lai YP et al (2016) Hypoxia suppresses myocardial survival pathway through HIF-1alpha-IGFBP-3-dependent signaling and enhances cardiomyocyte autophagic and apoptotic effects mainly via FoxO3a-induced BNIP3 expression. Growth Factors (Chur. Switzerland) 34:73–86

    Article  CAS  Google Scholar 

  26. Wu H, Huang S, Chen Z, Liu W, Zhou X, Zhang D (2015) Hypoxia-induced autophagy contributes to the invasion of salivary adenoid cystic carcinoma through the HIF-1alpha/BNIP3 signaling pathway. Mol Med Rep 12:6467–6474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hsieh DJ, Kuo WW, Lai YP et al (2015) 17beta-Estradiol and/or estrogen receptor beta attenuate the autophagic and apoptotic effects induced by prolonged hypoxia through HIF-1alpha-mediated BNIP3 and IGFBP-3 signaling blockage. Cell Physiol Biochem 36:274–284

    Article  CAS  PubMed  Google Scholar 

  28. Thongchot S, Yongvanit P, Loilome W et al (2014) High expression of HIF-1alpha, BNIP3 and PI3KC3: hypoxia-induced autophagy predicts cholangiocarcinoma survival and metastasis. Asian Pacific J Cancer Prev 15:5873–5878

    Article  Google Scholar 

  29. Rui L, Weiyi L, Yu M et al (2018) The serine/threonine protein kinase of Streptococcus suis serotype 2 affects the ability of the pathogen to penetrate the blood-brain barrier. Cell Microbiol 20:e12862

    Article  CAS  PubMed  Google Scholar 

  30. Zhu X, Zhou Y, Cai W, Sun H, Qiu L (2017) Salusin-beta mediates high glucose-induced endothelial injury via disruption of AMPK signaling pathway. Biochem Biophys Res Commun 491:515–521

    Article  CAS  PubMed  Google Scholar 

  31. Fiorentino TV, Prioletta A, Zuo P, Folli F (2013) Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases. Curr Pharm Des 19:5695–5703

    Article  CAS  PubMed  Google Scholar 

  32. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Rigothier C, Saleem MA, Bourget C, Mathieson PW, Combe C, Welsh GI (2016) Nuclear translocation of IQGAP1 protein upon exposure to puromycin aminonucleoside in cultured human podocytes: ERK pathway involvement. Cell Signal 28:1470–1478

    Article  CAS  PubMed  Google Scholar 

  34. Chavez-Valdez R, Martin LJ, Razdan S, Gauda EB, Northington FJ (2014) Sexual dimorphism in BDNF signaling after neonatal hypoxia-ischemia and treatment with necrostatin-1. Neuroscience 260:106–119

    Article  CAS  PubMed  Google Scholar 

  35. Wessels JM, Wu L, Leyland NA, Wang H, Foster WG (2014) The brain-uterus connection: brain derived neurotrophic factor (BDNF) and its receptor (Ntrk2) are conserved in the mammalian uterus. PloS one 9:e94036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Angelova PR, Abramov AY (2018) Role of mitochondrial ROS in the brain: from physiology to neurodegeneration. FEBS Lett 592:692–702

    Article  CAS  PubMed  Google Scholar 

  37. Yu T, Dohl J, Chen Y, Gasier HG, Deuster PA (2019) Astaxanthin but not quercetin preserves mitochondrial integrity and function, ameliorates oxidative stress, and reduces heat-induced skeletal muscle injury. J Cell Physiol. https://doi.org/10.1002/jcp.28006

    Article  PubMed  PubMed Central  Google Scholar 

  38. Kubli DA, Gustafsson AB (2012) Mitochondria and mitophagy: the yin and yang of cell death control. Circ Res 111:1208–1221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Anne Stetler R, Leak RK, Gao Y, Chen J (2013) The dynamics of the mitochondrial organelle as a potential therapeutic target. J Cereb Blood Flow Metab 33:22–32

    Article  CAS  PubMed  Google Scholar 

  40. Eyileten C, Kaplon-Cieslicka A, Mirowska-Guzel D (2017) Antidiabetic effect of brain-derived neurotrophic factor and its association with inflammation in type 2. Diabetes Mellit. 2017:2823671

    Google Scholar 

  41. Palikaras K, Tavernarakis N (2014) Mitochondrial homeostasis: the interplay between mitophagy and mitochondrial biogenesis. Exp Gerontol 56:182–188

    Article  CAS  PubMed  Google Scholar 

  42. Suzuki S, Koshimizu H, Adachi N et al (2017) Functional interaction between BDNF and mGluR II in vitro: BDNF down-regulated mGluR II gene expression and an mGluR II agonist enhanced BDNF-induced BDNF gene expression in rat cerebral cortical neurons. Peptides 89:42–49

    Article  CAS  PubMed  Google Scholar 

  43. Bathina S, Srinivas N, Das UN (2016) BDNF protects pancreatic beta cells (RIN5F) against cytotoxic action of alloxan, streptozotocin, doxorubicin and benzo(a)pyrene in vitro. Metabolism 65:667–684

    Article  CAS  PubMed  Google Scholar 

  44. Xiong W, Hua J, Liu Z et al (2018) PTEN induced putative kinase 1 (PINK1) alleviates angiotensin II-induced cardiac injury by ameliorating mitochondrial dysfunction. Int J Cardiol 266:198–205

    Article  PubMed  Google Scholar 

  45. Del Papa N, Pignataro F (2018) The role of endothelial progenitors in the repair of vascular damage in systemic sclerosis. Front Immunol 9:1383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Fang L, Li X, Zhong Y et al (2015) Autophagy protects human brain microvascular endothelial cells against methylglyoxal-induced injuries, reproducible in a cerebral ischemic model in diabetic rats. J Neurochem 135:431–440

    Article  CAS  PubMed  Google Scholar 

  47. Lv Q, Gu C, Chen C (2014) Venlafaxine protects methylglyoxal-induced apoptosis in the cultured human brain microvascular endothelial cells. Neurosci Lett 569:99–103

    Article  CAS  PubMed  Google Scholar 

  48. Kang J, Jia Z, Ping Y et al (2018) Testosterone alleviates mitochondrial ROS accumulation and mitochondria-mediated apoptosis in the gastric mucosa of orchiectomized rats. Arch Biochem Biophys 649:53–59

    Article  CAS  PubMed  Google Scholar 

  49. Zhou J, Wang H, Shen R et al (2018) Mitochondrial-targeted antioxidant MitoQ provides neuroprotection and reduces neuronal apoptosis in experimental traumatic brain injury possibly via the Nrf2-ARE pathway. Am J Transl Res 10:1887–1899

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Ma J, Zhao S, Gao G, Chang H, Ma P, Jin B (2015) Probucol protects against asymmetric dimethylarginine-induced apoptosis in the cultured human brain microvascular endothelial cells. J Mol Neurosci 57:546–553

    Article  CAS  PubMed  Google Scholar 

  51. Meek TH, Wisse BE, Thaler JP et al (2013) BDNF action in the brain attenuates diabetic hyperglycemia via insulin-independent inhibition of hepatic glucose production. Diabetes 62:1512–1518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Liu Y, Tao L, Fu X, Zhao Y, Xu X (2013) BDNF protects retinal neurons from hyperglycemia through the TrkB/ERK/MAPK pathway. Mol Med Rep 7:1773–1778

    Article  CAS  PubMed  Google Scholar 

  53. Jiang H, Huang S, Li X, Li X, Zhang Y, Chen ZY (2015) Tyrosine kinase receptor B protects against coronary artery disease and promotes adult vasculature integrity by regulating Ets1-mediated VE-cadherin expression. Arterioscler Thromb Vasc Biol 35:580–588

    Article  CAS  PubMed  Google Scholar 

  54. Monnier A, Prigent-Tessier A, Quirie A et al (2017) Brain-derived neurotrophic factor of the cerebral microvasculature: a forgotten and nitric oxide-dependent contributor of brain-derived neurotrophic factor in the brain. Acta Physiolo (Oxford England) 219:790–802

    Article  CAS  Google Scholar 

  55. Meuchel LW, Thompson MA, Cassivi SD, Pabelick CM, Prakash YS (2011) Neurotrophins induce nitric oxide generation in human pulmonary artery endothelial cells. Cardiovasc Res 91:668–676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Han X, Wang B, Sun Y et al (2018) Metformin modulates high glucose-incubated human umbilical vein endothelial cells proliferation and apoptosis through AMPK/CREB/BDNF pathway. Front Pharmacol 9:1266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Yu F, Liu Y, Xu J (2018) Pro-BDNF contributes to hypoxia/reoxygenation injury in myocardial microvascular endothelial cells: roles of receptors p75(NTR) and sortilin and activation of JNK and Caspase 3. 2018:3091424

  58. Saito T, Sadoshima J (2015) Molecular mechanisms of mitochondrial autophagy/mitophagy in the heart. Circ Res 116:1477–1490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Liu L, Sakakibara K, Chen Q, Okamoto K (2014) Receptor-mediated mitophagy in yeast and mammalian systems. Cell Res 24:787–795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Xu Z, Lv XA, Dai Q, Lu M, Jin Z (2018) Exogenous BDNF increases mitochondrial pCREB and alleviates neuronal metabolic defects following mechanical injury in a MPTP-dependent way. Mol Neurobiol 55:3499–3512

    Article  CAS  PubMed  Google Scholar 

  61. Wu CL, Chen SD, Yin JH, Hwang CS, Yang DI (2016) Nuclear factor-kappaB-dependent Sestrin2 induction mediates the antioxidant effects of BDNF against mitochondrial inhibition in rat cortical neurons. Mol Neurobiol 53:4126–4142

    Article  CAS  PubMed  Google Scholar 

  62. Ma WQ, Sun XJ, Wang Y, Zhu Y, Han XQ, Liu NF (2018) Restoring mitochondrial biogenesis with metformin attenuates beta-GP-induced phenotypic transformation of VSMCs into an osteogenic phenotype via inhibition of PDK4/oxidative stress-mediated apoptosis. Mol Cell Endocrinol, 479:39–53

    Google Scholar 

  63. Nikoletopoulou V, Sidiropoulou K, Kallergi E, Dalezios Y, Tavernarakis N (2017) Modulation of autophagy by BDNF underlies synaptic plasticity. Cell Metab 26:230–242.e235

    Article  CAS  PubMed  Google Scholar 

  64. Song X, Liu B, Cui L et al (2017) Silibinin ameliorates anxiety/depression-like behaviors in amyloid beta-treated rats by upregulating BDNF/TrkB pathway and attenuating autophagy in hippocampus. Physiol Behav 179:487–493

    Article  CAS  PubMed  Google Scholar 

  65. Mazouffre C, Geyl S, Perraud A et al (2017) Dual inhibition of BDNF/TrkB and autophagy: a promising therapeutic approach for colorectal cancer. 21:2610–2622

  66. Catrina SB (2014) Impaired hypoxia-inducible factor (HIF) regulation by hyperglycemia. J Mol Med (Berlin Germany) 92:1025–1034

    Article  CAS  Google Scholar 

  67. Yu WY, Sun W, Yu DJ, Zhao TL, Wu LJ, Zhuang HR (2018) Adipose-derived stem cells improve neovascularization in ischemic flaps in diabetic mellitus through HIF-1alpha/VEGF pathway. Eur Rev Med Pharmacol Sci 22:10–16

    PubMed  Google Scholar 

  68. Krishan P, Singh G, Bedi O (2017) Carbohydrate restriction ameliorates nephropathy by reducing oxidative stress and upregulating HIF-1alpha levels in type-1 diabetic rats. J Diabetes Metab Disorders 16:47

    Article  CAS  Google Scholar 

  69. Lin CY, Hung SY, Chen HT et al (2014) Brain-derived neurotrophic factor increases vascular endothelial growth factor expression and enhances angiogenesis in human chondrosarcoma cells. Biochem Pharmacol 91:522–533

    Article  CAS  PubMed  Google Scholar 

  70. Chourasia AH, Tracy K, Frankenberger C et al (2015) Mitophagy defects arising from BNip3 loss promote mammary tumor progression to metastasis. EMBO Rep 16:1145–1163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Song J, Yoon D, Christensen RD, Horvathova M, Thiagarajan P, Prchal JT (2015) HIF-mediated increased ROS from reduced mitophagy and decreased catalase causes neocytolysis. J Mol Med (Berlin Germany) 93:857–866

    Article  CAS  Google Scholar 

  72. Segers VFM, Brutsaert DL, De Keulenaer GW (2018) Cardiac remodeling: endothelial cells have more to say than just NO. Front Physiol 9:382

    Article  PubMed  PubMed Central  Google Scholar 

  73. Hu J, Wang S, Xiong Z et al (2018) Exosomal Mst1 transfer from cardiac microvascular endothelial cells to cardiomyocytes deteriorates diabetic cardiomyopathy. Biochim Biophys Acta Mol Basis Dis 1864:3639–3649

    Article  CAS  PubMed  Google Scholar 

  74. Sniegon I, Priess M, Heger J, Schulz R, Euler G (2017) Endothelial mesenchymal transition in hypoxic microvascular endothelial cells and paracrine induction of cardiomyocyte apoptosis are mediated via TGFbeta(1)/SMAD signaling. Int J Mol Sci 18:2290

    Article  CAS  PubMed Central  Google Scholar 

  75. Wang F, Jia J, Lal N et al (2016) High glucose facilitated endothelial heparanase transfer to the cardiomyocyte modifies its cell death signature. Cardiovasc Res 112:656–668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Duh EJ, Sun JK, Stitt AW (2017) Diabetic retinopathy: current understanding, mechanisms, and treatment strategies. JCI Insight 2

Download references

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).

Author information

Author notes

  1. Hong Jin and Yi Zhu have contributed equally to this study.

Authors and Affiliations

  1. Department of Cardiology, School of Medicine, Zhongda Hospital, Southeast University, Nanjing, 210009, People’s Republic of China

    Hong Jin, Yi Zhu, Yiping Li, Wenqi Ma, Xiqiong Han & Bilei Wang

  2. Nanjing Ninghai Middle School, Nanjing, 210009, People’s Republic of China

    Xiuyu Ding

Authors
  1. Hong Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yi Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yiping Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiuyu Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wenqi Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiqiong Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bilei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hong Jin.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 888 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jin, H., Zhu, Y., Li, Y. et al. BDNF-mediated mitophagy alleviates high-glucose-induced brain microvascular endothelial cell injury. Apoptosis 24, 511–528 (2019). https://doi.org/10.1007/s10495-019-01535-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10495-019-01535-x

Keywords

Search

Navigation