Tyrosine kinase Fyn promotes apoptosis after intracerebral hemorrhage in rats by activating Drp1 signaling

Zhang, Li; Wang, Lu; Xiao, Han; Gan, Hui; Chen, Hui; Zheng, Shuyue; Jian, Dan; Zhai, Xuan; Jiang, Ning; Zhao, Jing; Liang, Ping

doi:10.1007/s00109-020-02022-6

Cited by 9 publications

(17 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some studies have pointed out that cerebral hemorrhage causes brain edema, produces inflammatory damage, destroys the blood–brain barrier (BBB), increases intracranial pressure, and eventually leads to nerve cell necrosis (Yang J. & Wang, 2021 ; Zhang L. et al., 2021 ). Accumulated evidence has shown that early brain injury (EBI) induced by microglia activation releases a large number of inflammatory cytokines, which can be used as a key indicator of the inflammatory response in the brain (Li P., Li X. et al., 2020 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Protective mechanism of FoxO1 against early brain injury after subarachnoid hemorrhage by regulating autophagy

et al. 2021

View full text Add to dashboard Cite

Introduction:Early brain injury (EBI) plays a key role in the devastating outcomes after subarachnoid hemorrhage (SAH). Autophagy and apoptosis may share a common molecular inducer that regulates the process of cell death. FoxO1, as a key regulator of neuronal autophagy which is involved in apoptosis, has not been reported in SAH rats.This work was to investigate the protective and anti-inflammatory effects of FoxO1 on EBI after SAH by regulating autophagy. Methods:In this study, we constructed the SAH model. In experiment I, low dose (50 μl of 1 × 10 8 IU/ml) or high dose (50 μl of 1 × 10 10 IU/ml) of FoxO1 gene overexpressed adenovirus vector was injected into the lateral ventricle of rats before SAH. In experiment II, we reported the effect of FoxO1 overexpress on nerve function recovery, oedema, BBB leakage, neuronal death in rats after SAH through autophagy regulation.Post-SAH evaluation included neurological function score, brain water content, evans blue exosmosis, pathological changes, inflammatory response and apoptosis. Results:The experiment I showed that either low or high dose of ad-FoxO1 could significantly improve nerve function, reduce cerebral water content and reduce bloodbrain barrier (BBB) destruction in rats, indicating that ad-FoxO1 had a protective effect on brain injury in rats EBI after SAH. In addition, ad-FoxO1 promoted autophagy in rat hippocampal tissue, as evidenced by accumulation of LC3II/I and Beclin-1 and degradation of p62. Furthermore, ad-FoxO1 inhibited the inflammatory response and apoptosis of rat hippocampal neurons after SAH. The experiment II showed that both ad-FoxO1 and rapamycin attenuated the injury of nerve function in rats after SAH, and this synergistic effect further reduced cerebral edema and evansblue extravasation, decreased hippocampus neuronal cell apoptosis, and declined inflammatory response.However, this was contrary to the results of chloroquine. These findings suggested that FoxO1 regulated the neural function of EBI after SAH through the autophagy pathway. Conclusions:The findings in this study was beneficial for identifying the novel therapeutic target for the treatment of SAH.

show abstract

Section: Introductionmentioning

confidence: 99%

“…Some studies have pointed out that cerebral hemorrhage causes brain edema, produces inflammatory damage, destroys the blood-brain barrier (BBB), increases intracranial pressure, and eventually leads to nerve cell necrosis (Yang J. & Wang, 2021;Zhang L. et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Protective mechanism of FoxO1 against early brain injury after subarachnoid hemorrhage by regulating autophagy

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Notably, a synergistic protective effect of mitochondria‐targeted antioxidant SS31 and Mdivi1 was reported against Aβ induced cell death in neurons (Reddy et al, 2018). Moreover, tyrosine kinase‐mediated apoptosis during intracerebral haemorrhage depends on the Drp1 phosphorylation at Ser616 (Zhang, Wang, et al, 2021). Several other reports supported the mechanistic implications of Drp1 in intracerebral haemorrhage and subarachnoid haemorrhage (Fan et al, 2017; Flippo et al, 2020; Grohm et al, 2012; Wu et al, 2017, 2020).…”

Section: Drp1 Function In the Brainmentioning

confidence: 99%

Mechanistic and therapeutic role of Drp1 in the pathogenesis of Alzheimer's disease

Bera

Lavanya

Reshmi

et al. 2022

Eur J of Neuroscience

View full text Add to dashboard Cite

Alzheimer's disease (AD), a progressive neurodegenerative disorder, has emerged as the most common form of dementia in the elderly. Two major pathological hallmarks have been identified for AD: extracellular amyloid plaques and intracellular neurofibrillary tangles (NFT). Recently, dynaminrelated protein 1 (Drp1) was recognized to contribute significantly towards the pathogenesis of AD. Drp1 is primarily located in the cytosol, from where it translocates to the mitochondrial outer membrane and drives the mitochondrial fission via GTP hydrolysis. Drp1 interacts with Aβ and phosphorylated tau, leading to excessive mitochondrial fragmentation, which in turn results in synaptic dysfunction, neuronal damage and cognitive decline. Several studies suggest an increase in the level of Drp1 in the post-mortem brain specimen collected from the AD patients and murine models of AD. Interestingly, heterozygous deletion of Drp1 in the transgenic murine model of AD ameliorates the mitochondrial dysfunction, improving learning and memory. The current review article discusses the possible mechanistic pathways by which Drp1 can influence the pathogenesis of AD. Besides, it will describe various inhibitors for Drp1 and their potential role as therapeutics for AD in the future.

show abstract

“…The Drp1 inhibitor Mdivi-1 (Mitochondrial division inhibitor 1) can reverse the proapoptosis induced by Fyn overexpression. Fyn activates Drp1 signaling by phosphorylating 616 serine in Drp1 to increase neuronal apoptosis in rats after intracerebral hemorrhage [ 59 ].…”

Section: Neuroexcitotoxicity and Fynmentioning

confidence: 99%

“…Experiments in the adult rat middle cerebral artery occlusion (MCAO) model showed that PP2 reduced infarct volume and Blood-Brain Barrier (BBB) leakage [ 99 ]. PP2 blocks ET-1-induced elevation of IL-6 [ 59 ]. However, the mechanism of PP2 in alleviating cerebral ischemia-reperfusion injury has not been fully elucidated.…”

Section: The Potential Of Fyn As a Therapeutic Target For Strokementioning

confidence: 99%

Fyn Signaling in Ischemia-Reperfusion Injury: Potential and Therapeutic Implications

Tang

et al. 2022

Mediators of Inflammation

View full text Add to dashboard Cite

Ischemic stroke caused by arterial occlusion is the most common type of stroke and is one of the leading causes of disability and death, with the incidence increasing each year. Fyn is a nonreceptor tyrosine kinase belonging to the Src family of kinases (SFKs), which is related to many normal and pathological processes of the nervous system, including neurodevelopment and disease progression. In recent years, more and more evidence suggests that Fyn may be closely related to cerebral ischemia-reperfusion, including energy metabolism disorders, excitatory neurotoxicity, intracellular calcium homeostasis, free radical production, and the activation of apoptotic genes. This paper reviews the role of Fyn in the pathological process of cerebral ischemia-reperfusion, including neuroexcitotoxicity and neuroinflammation, to explore how Fyn affects specific signal cascades and leads to cerebral ischemia-reperfusion injury. In addition, Fyn also promotes the production of superoxide and endogenous NO, so as to quickly react to produce peroxynitrite, which may also mediate cerebral ischemia-reperfusion injury, which is discussed in this paper. Finally, we revealed the treatment methods related to Fyn inhibitors and discussed its potential as a clinical treatment for ischemic stroke.

show abstract

Tyrosine kinase Fyn promotes apoptosis after intracerebral hemorrhage in rats by activating Drp1 signaling

Cited by 9 publications

References 48 publications

Protective mechanism of FoxO1 against early brain injury after subarachnoid hemorrhage by regulating autophagy

Protective mechanism of FoxO1 against early brain injury after subarachnoid hemorrhage by regulating autophagy

Mechanistic and therapeutic role of Drp1 in the pathogenesis of Alzheimer's disease

Fyn Signaling in Ischemia-Reperfusion Injury: Potential and Therapeutic Implications

Contact Info

Product

Resources

About