Mdivi-1 alleviates blood-brain barrier disruption and cell death in experimental traumatic brain injury by mitigating autophagy dysfunction and mitophagy activation

Wu, Qiong; Gao, Cheng; Wang, Haochen; Zhang, Xinmu; Li, Qianqian; Gu, Zhiya; Shi, Xiaolan; Cui, Yongchun; Wang, Tao; Chen, Xiping; Wang, Xin; Luo, Chengliang; Tao, Luyang

doi:10.1016/j.biocel.2017.11.007

Cited by 77 publications

(49 citation statements)

References 42 publications

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“…However, the protective effects of PD against mitochondria-dependent apoptosis were ablated by depleting Parkin and Atg7. To further confirm the role of mitophagy on PD-induced protection against lung injury, we used mdivi-1, a known inhibitor of mitochondrial fission, to inhibit mitophagy in vivo [33,34].…”

Section: Discussionmentioning

confidence: 99%

Polydatin mediates Parkin-dependent mitophagy and protects against mitochondria-dependent apoptosis in acute respiratory distress syndrome

Liu

et al. 2019

Laboratory Investigation

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Mitophagy removes dysfunctional mitochondria and is known to play an important role in the pathogenesis of several diseases; however, the role of mitophagy in acute respiratory distress syndrome (ARDS) remains poorly understood. While we have previously demonstrated that polydatin (PD) improves lipopolysaccharide (LPS)-induced ARDS, the specific mechanism remains unclear. In present study, we aimed to determine whether PD activates Parkin-dependent mitophagy to protect against LPS-induced mitochondria-dependent apoptosis and lung injury. To establish the ARDS model, C57BL/6 mice were intratracheally injected with LPS (5 mg/kg) in vivo and Beas-2B cells were exposured to 0.5 mM LPS in vitro. Our results indicate that PD facilitates Parkin translocation to mitochondria and promotes mitophagy in ARDS-challenged mice and LPS-treated Beas-2B cells. However, PD-induced mitophagy was suppressed in Parkin−/− mice and Parkin siRNA transfected cells, indicating that PD activates Parkin-dependent mitophagy. Furthermore, the protective effects of PD against LPS-induced mitochondria-dependent apoptosis and lung injury were suppressed when Parkin was depleted both in vivo and in vitro. The inhibition of mitophagy with mitophagy inhibitor mitochondrial division inhibitor-1 in vivo and silencing of autophagy-related gene 7 in vitro also blocked the protective effects mediated by PD. Our data suggest that Parkin-dependent mitophagy induced by PD provides protection against mitochondria-dependent apoptosis in ARDS.

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Section: Discussionmentioning

confidence: 99%

Polydatin mediates Parkin-dependent mitophagy and protects against mitochondria-dependent apoptosis in acute respiratory distress syndrome

Liu

et al. 2019

Laboratory Investigation

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“…Hence, mitophagy can alleviate secondary brain injuries by selective degradation of damaged mitochondria after TBI [289]. Wu et al [290] have used mitochondrial division inhibitor-1 (Mdivi-1) to inhibit the key regulator of mitochondrial fission, Drp1, and have reported that it can extenuate TBI-induced blood-brain barrier (BBB) disruption and cell death by inhibiting dysfunctional autophagy, but by activating mitophagy. Likewise, Liu et al [291] have reported increased mitophagy after TBI, which diminished the TBI-mediated intestinal epithelial cell damage, and improved intestinal permeability via ERK/Nrf2/HO-1 signaling.…”

Section: Traumatic Brain Injurymentioning

confidence: 99%

Selective autophagy as a therapeutic target for neurological diseases

Ocak

Gao

et al. 2020

Cell. Mol. Life Sci.

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The neurological diseases primarily include acute injuries, chronic neurodegeneration, and others (e.g., infectious diseases of the central nervous system). Autophagy is a housekeeping process responsible for the bulk degradation of misfolded protein aggregates and damaged organelles through the lysosomal machinery. Recent studies have suggested that autophagy, particularly selective autophagy, such as mitophagy, pexophagy, ER-phagy, ribophagy, lipophagy, etc., is closely implicated in neurological diseases. These forms of selective autophagy are controlled by a group of important proteins, including PTEN-induced kinase 1 (PINK1), Parkin, p62, optineurin (OPTN), neighbor of BRCA1 gene 1 (NBR1), and nuclear fragile X mental retardation-interacting protein 1 (NUFIP1). This review highlights the characteristics and underlying mechanisms of different types of selective autophagy, and their implications in various forms of neurological diseases.

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“…Recently, there were some other autophagy activators or inhibitors that have been proposed in TBI models such as pifithrin-α (PFT-α; Huang Y.-N. et al, 2018 ), apocynin (Feng et al, 2017a ), trehalose (Portbury et al, 2017 ), dexmedetomidine (Shen et al, 2017 ), mitochondrial division inhibitor 1 (Mdivi-1; Wu et al, 2018 ) and so on (Wang et al, 2013 ; Cui et al, 2014 , 2015 , 2017 ; Lin et al, 2014 ; Zhang et al, 2014 ; Jin et al, 2015 ; Ma et al, 2015 ; Yao et al, 2015 ; Du et al, 2016 ; Zhang L. et al, 2016 ; Zhao et al, 2016 ; Sun et al, 2017 ). All these agents exerted neuroprotective effects in models of TBI, possibly by activation or inhibition of autophagy.…”

Section: Related Therapeutics Agents Targeting Autophagy In Tbimentioning

confidence: 99%

Autophagy in Traumatic Brain Injury: A New Target for Therapeutic Intervention

Zhang

Wang

2018

Front. Mol. Neurosci.

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Traumatic brain injury (TBI) is one of the most devastating forms of brain injury. Many pathological mechanisms such as oxidative stress, apoptosis and inflammation all contribute to the secondary brain damage and poor outcomes of TBI. Current therapies are often ineffective and poorly tolerated, which drive the explore of new therapeutic targets for TBI. Autophagy is a highly conserved intracellular mechanism during evolution. It plays an important role in elimination abnormal intracellular proteins or organelles to maintain cell stability. Besides, autophagy has been researched in various models including TBI. Previous studies have deciphered that regulation of autophagy by different molecules and pathways could exhibit anti-oxidative stress, anti-apoptosis and anti-inflammation effects in TBI. Hence, autophagy is a promising target for further therapeutic development in TBI. The present review provides an overview of current knowledge about the mechanism of autophagy, the frequently used methods to monitor autophagy, the functions of autophagy in TBI as well as its potential molecular mechanisms based on the pharmacological regulation of autophagy.

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Mdivi-1 alleviates blood-brain barrier disruption and cell death in experimental traumatic brain injury by mitigating autophagy dysfunction and mitophagy activation

Cited by 77 publications

References 42 publications

Polydatin mediates Parkin-dependent mitophagy and protects against mitochondria-dependent apoptosis in acute respiratory distress syndrome

Polydatin mediates Parkin-dependent mitophagy and protects against mitochondria-dependent apoptosis in acute respiratory distress syndrome

Selective autophagy as a therapeutic target for neurological diseases

Autophagy in Traumatic Brain Injury: A New Target for Therapeutic Intervention

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