A novel mechanism linking ferroptosis and endoplasmic reticulum stress via the circPtpn14/miR-351-5p/5-LOX signaling in melatonin-mediated treatment of traumatic brain injury

Wu, Chenrui; Du, Mengran; Yu, Renqiang; Cheng, Yuqi; Wu, Biying; Fu, Jiayuanyuan; Tan, Weilin; Zhou, Qiang; Balawi, Ehab; Liao, Zhengbu

doi:10.1016/j.freeradbiomed.2021.12.007

Cited by 53 publications

(28 citation statements)

References 89 publications

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“…Studies have indicated that Mel can act against inflammation (Dehghan et al, 2018), alleviate oxidative damage (Salman et al, 2021), and inhibit neuronal apoptosis (Wu et al, 2016) in TBI. Moreover, Wu et al (2022) in our group indicated the potential mechanism of Mel on anti-ferroptosis in TBI. Yet, the concrete protective mechanism of Mel in TBI is still not fully understood.…”

Section: Introductionmentioning

confidence: 75%

“…Jiang et al (2019) profiled 191 differentially expressed circRNAs in the CCI model, which may be related to inflammation, cell death, and repair of damage. The previous study of our group revealed the protective role of circLphn3 in the bloodbrain barrier after TBI (Cheng et al, 2022) and identified the circPtpn14/miR-351-5p/5-LOX axis might be a new mechanism regulating the effect of Mel against TBI (Wu et al, 2022), in addition, we found that to inhibit circIgfbp2 could alleviate the synapse dysfunction caused by mitochondrial dysfunction and oxidative stress through the miR-370-3p/BACH1/HO-1 axis after TBI (Du et al, 2022). Nevertheless, there is a lack of studies investigating the transcriptomics analysis of Mel intervention in TBI.…”

Section: Introductionmentioning

confidence: 81%

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Protective effects and regulatory pathways of melatonin in traumatic brain injury mice model: Transcriptomics and bioinformatics analysis

Zhou

et al. 2022

Front. Mol. Neurosci.

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Traumatic brain injury (TBI) is the leading cause of disability and mortality globally. Melatonin (Mel) is a neuroendocrine hormone synthesized from the pineal gland that protects against TBI. Yet, the precise mechanism of action is not fully understood. In this study, we examined the protective effect and regulatory pathways of melatonin in the TBI mice model using transcriptomics and bioinformatics analysis. The expression profiles of mRNA, long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA) were constructed using the whole transcriptomes sequencing technique. In total, 93 differentially expressed (DE) mRNAs (DEmRNAs), 48 lncRNAs (DElncRNAs), 59 miRNAs (DEmiRNAs), and 59 circRNAs (DEcircRNAs) were identified by the TBI mice with Mel treatment compared to the group without drug intervention. The randomly selected coding RNAs and non-coding RNAs (ncRNAs) were identified by quantitative real-time polymerase chain reaction (qRT-PCR). To further detect the biological functions and potential pathways of those differentially expressed RNAs, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were executed. In our research, the regulatory network was constructed to show the relationship of lncRNA-RBPs. The lncRNA-mRNA co-expression network was established based on the Pearson coefficient to indicate the expression correlations. Moreover, the DEcircRNA–DEmiRNA–DEmRNA and DElncRNA–DEmiRNA–DEmRNA regulatory networks were constructed to demonstrate the regulatory relationship between ncRNAs and mRNA. Finally, to further verify our predicted results, cytoHubba was used to find the hub gene in the synaptic vesicle cycle pathway, and the expression level of SNAP-25 and VAMP-2 after melatonin treatment were detected by Western blotting and immunofluorescence. To sum up, these data offer a new insight regarding the molecular effect of melatonin treatment after TBI and suggest that the high-throughput sequencing and analysis of transcriptomes are useful for studying the drug mechanisms in treatment after TBI.

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Section: Introductionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 81%

Protective effects and regulatory pathways of melatonin in traumatic brain injury mice model: Transcriptomics and bioinformatics analysis

Zhou

et al. 2022

Front. Mol. Neurosci.

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“…CircIgfbp2 is significantly up-regulated after TBI in mice and in H 2 O 2 -treated HT22 cells The expression profiles of circRNAs are changed after TBI [21,22], but the involvement of specific circRNAs in neuropsychological impairment after TBI remains unclear. In order to examine the differentially expressed circRNAs after TBI, we collected three pairs of sham and traumatic mouse brain specimens and conducted the RNA-Seq (PRJNA725662).…”

Section: Resultsmentioning

confidence: 99%

A novel circular RNA, circIgfbp2, links neural plasticity and anxiety through targeting mitochondrial dysfunction and oxidative stress-induced synapse dysfunction after traumatic brain injury

et al. 2022

Mol Psychiatry

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Traumatic brain injury (TBI) can lead to different neurological and psychiatric disorders. Circular RNAs (circRNAs) are highly expressed in the nervous system and enriched in synapses; yet, the underlying role and mechanisms of circRNAs in neurological impairment and dysfunction are still not fully understood. In this study, we investigated the expression of circRNAs and their relation with neurological dysfunction after TBI. RNA-Seq was used to detect differentially expressed circRNAs in injured brain tissue, revealing that circIgfbp2 was significantly increased. Up-regulated hsa_circ_0058195, which was highly homologous to circIgfbp2, was further confirmed in the cerebral cortex specimens and serum samples of patients after TBI. Moreover, correlation analysis showed a positive correlation between hsa_circ_0058195 levels and the Self-Rating Anxiety Scale scores in these subjects. Furthermore, knockdown of circIgfbp2 in mice relieved anxiety-like behaviors and sleep disturbances induced by TBI. Knockdown of circIgfbp2 in H2O2 treated HT22 cells alleviated mitochondrial dysfunction, while its overexpression reversed the process. Mechanistically, we discovered that circIgfbp2 targets miR-370-3p to regulate BACH1, and down-regulating BACH1 alleviated mitochondrial dysfunction and oxidative stress-induced synapse dysfunction. In conclusion, inhibition of circIgfbp2 alleviated mitochondrial dysfunction and oxidative stress-induced synapse dysfunction after TBI through the miR-370-3p/BACH1/HO-1 axis. Thus, circIgfbp2 might be a novel therapeutic target for anxiety and sleep disorders after TBI.

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“…However, melatonin did not exert a neuroprotective effect in a mouse TBI model with knockout of neuronal Fth . Through both in vivo and in vitro experiments, Wu et al [ 107 ] demonstrated that melatonin significantly improved brain function in mice after TBI by attenuating ferroptosis and ERS and alleviating lipid peroxidation via circPtpn14/miR-351-5p/5-LOX signaling. Taken together, these findings suggest that melatonin is an effective ferroptosis inhibitor.…”

Section: Ferroptosis-based Treatment Of Tbimentioning

confidence: 99%

Mechanism of Ferroptosis and Its Relationships with Other Types of Programmed Cell Death: Insights for Potential Therapeutic Benefits in Traumatic Brain Injury

Pang

Zheng

Ren

et al. 2022

Oxidative Medicine and Cellular Longevity

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Traumatic brain injury (TBI) is a serious health issue with a high incidence, high morbidity, and high mortality that poses a large burden on society. Further understanding of the pathophysiology and cell death models induced by TBI may support targeted therapies for TBI patients. Ferroptosis, a model of programmed cell death first defined in 2012, is characterized by iron dyshomeostasis, lipid peroxidation, and glutathione (GSH) depletion. Ferroptosis is distinct from apoptosis, autophagy, pyroptosis, and necroptosis and has been shown to play a role in secondary brain injury and worsen long-term outcomes after TBI. This review systematically describes (1) the regulatory pathways of ferroptosis after TBI, (2) the neurobiological links between ferroptosis and other cell death models, and (3) potential therapies targeting ferroptosis for TBI patients.

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A novel mechanism linking ferroptosis and endoplasmic reticulum stress via the circPtpn14/miR-351-5p/5-LOX signaling in melatonin-mediated treatment of traumatic brain injury

Cited by 53 publications

References 89 publications

Protective effects and regulatory pathways of melatonin in traumatic brain injury mice model: Transcriptomics and bioinformatics analysis

Protective effects and regulatory pathways of melatonin in traumatic brain injury mice model: Transcriptomics and bioinformatics analysis

A novel circular RNA, circIgfbp2, links neural plasticity and anxiety through targeting mitochondrial dysfunction and oxidative stress-induced synapse dysfunction after traumatic brain injury

Mechanism of Ferroptosis and Its Relationships with Other Types of Programmed Cell Death: Insights for Potential Therapeutic Benefits in Traumatic Brain Injury

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