iTRAQ-Based Quantitative Proteomics Reveals the New Evidence Base for Traumatic Brain Injury Treated with Targeted Temperature Management

Cheng, Shi-Xiang; Xu, Zhongwei; Yi, Tailong; Sun, Haitao; Cheng, Yang; Yu, Zhen; Yang, Xiaosa; Jin, Xiaojuan; Tu, Yue; Zhang, Sai

doi:10.1007/s13311-017-0591-2

Cited by 24 publications

(24 citation statements)

References 61 publications

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“…FB23-2 can inhibit the m6A demethylase FTO, and it has been confirmed in leukemia studies that the degree of m6A methylation is reduced after intraperitoneal injection of FTO [33]. In the mNSS experiments, the neurological function of rats after TBI presents a tendency to restore itself, which is in agreement with previous studies [56]. However, the self-healing phenomenon was not found in FB23-2-injected TBI rats, indicating that functional FTO is necessary to repair neurological damage caused by TBI.…”

Section: Discussionsupporting

confidence: 89%

Epitranscriptomic profiling of N6-methyladenosine-related RNA methylation in rat cerebral cortex following traumatic brain injury

Zhang

et al. 2020

Mol Brain

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Background: N6-methyladenosine (m6A) is the most prevalent post-transcriptional modification of eukaryotic mRNA. It has been reported that there is a stimulus-dependent regulation of m6A in the mammalian central nervous system in response to sensory experience, learning, and injury. The mRNA m6A methylation pattern in rat cortex after traumatic brain injury (TBI) has not been investigated. Results: In this study, we conducted a genome-wide profiling of mRNA m6A methylation in rat cortex via methylated RNA immunoprecipitation sequencing (MeRIP-Seq). After TBI, the expressions of METTL14 and FTO were significantly down-regulated in rat cerebral cortex. Using MeRIP-Seq, we identified a total of 2165 significantly changed peaks, of which 1062 were significantly up-regulated and 1103 peaks were significantly down-regulated. These m6A peaks were located across 1850 genes. The analysis of both m6A peaks and mRNA expression revealed that there were 175 mRNA significantly altered methylation and expression levels after TBI. Moreover, it was found that functional FTO is necessary to repair neurological damage caused by TBI but has no effect on the spatial learning and memory abilities of TBI rats by using FTO inhibitor FB23-2.Conclusion: This study explored the m6A methylation pattern of mRNA after TBI in rat cortex and identified FTO as possible intervention targets in the epigenetic modification of TBI.

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Section: Discussionsupporting

confidence: 89%

Epitranscriptomic profiling of N6-methyladenosine-related RNA methylation in rat cerebral cortex following traumatic brain injury

Zhang

et al. 2020

Mol Brain

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“…Using a combination of an in-vitro stretch model, a rat CCI model and CSF from TBI patients, Cheng et al [ 2 ▪▪ ] investigated the influence of hypothermia on response to TBI. The proteomics portion of this study involved an examination of the influence of hypothermia after CCI.…”

Section: Progress To Date In 2018mentioning

confidence: 99%

Proteomic changes in traumatic brain injury: experimental approaches

Sowers¹,

Zhang³

et al. 2018

Current Opinion in Neurology

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Purpose of reviewThe underlying mechanisms responsible for chronic and progressive neurological damage after traumatic brain injury (TBI) are poorly understood, and therefore, current treatment options are limited. Proteomics is an emerging methodology to study changes to the TBI proteome in both patients and experimental models.Recent findingsAlthough experimentally complex, mass spectrometry-based proteomics approaches are converging on a set of common methods. However, these methods are being applied to an increasingly diverse range of experimental models and types of injury.SummaryIn this review, our aim is to briefly describe experimental TBI models and the underlying methods common to most proteomic approaches. We will then review a series of articles that have recently appeared in which these approaches have been applied to important TBI questions. We will summarize several recent experimental studies, and suggest how the results of these emerging studies might impact future research as well as patient treatment.

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“…As for TBI, proteomics has been primarily applied to discover new biomarkers [ 41 , 42 ]. In particular, Cheng et al found that targeted temperature management (TTM) prevented TBI-induced neuronal necrosis, neuronal death, and brain edema, and some altered proteins (i.e., plasminogen, antithrombin III, and transthyretin) were identified [ 43 ]. Wu et al detected protein changes in the traumatically injured hippocampus and found that pathways associated with global energy metabolism were significantly downregulated [ 44 ].…”

Section: Introductionmentioning

confidence: 99%

iTRAQ-based proteomic profiling reveals protein alterations after traumatic brain injury and supports thyroxine as a potential treatment

Zhang

Wang

et al. 2021

Mol Brain

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Traumatic brain injury (TBI) is a primary cause of disability and death across the world. Previously, RNA analysis was widely used to study the pathophysiological mechanisms underlying TBI; however, the relatively low correlation between the transcriptome and proteome revealed that RNA transcription abundance does not reliably predict protein abundance, which led to the emergence of proteomic research. In this study, an iTRAQ proteomics approach was applied to detect protein alterations after TBI on a large scale. A total of 3937 proteins were identified, and 146 proteins were significantly changed after TBI. Moreover, 23 upregulated proteins were verified by parallel reaction monitoring (PRM), and fold changes in 16 proteins were consistent with iTRAQ outcomes. Transthyretin (Ttr) upregulation has been demonstrated at the transcriptional level, and this study further confirmed this at the protein level. After treatment with thyroxine (T4), which is transported by Ttr, the effects of T4 on neuronal histopathology and behavioral performance were determined in vivo (TBI + T4 group). Brain edema was alleviated, and the integrity of the blood brain barrier (BBB) improved. Escape latency in the Morris water maze (MWM) declined significantly compared with the group without T4 treatment. Modified neurological severity scores (mNSS) of the TBI + T4 group decreased from day 1 to day 7 post-TBI compared with the TBI + saline group. These results indicate that T4 treatment has potential to alleviate pathologic and behavioral abnormalities post-TBI. Protein alterations after T4 treatment were also detected by iTRAQ proteomics. Upregulation of proteins like Lgals3, Gfap and Apoe after TBI were reversed by T4 treatment. GO enrichment showed T4 mainly affected intermediate filament organization, cholesterol transportation and axonal regeneration. In summary, iTRAQ proteomics provides information about the impact of TBI on protein alterations and yields insight into underlying mechanisms and pathways involved in TBI and T4 treatment. Finally, Ttr and other proteins identified by iTRAQ may become potential novel treatment targets post-TBI.

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iTRAQ-Based Quantitative Proteomics Reveals the New Evidence Base for Traumatic Brain Injury Treated with Targeted Temperature Management

Cited by 24 publications

References 61 publications

Epitranscriptomic profiling of N6-methyladenosine-related RNA methylation in rat cerebral cortex following traumatic brain injury

Epitranscriptomic profiling of N6-methyladenosine-related RNA methylation in rat cerebral cortex following traumatic brain injury

Proteomic changes in traumatic brain injury: experimental approaches

iTRAQ-based proteomic profiling reveals protein alterations after traumatic brain injury and supports thyroxine as a potential treatment

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