Role of activating transcription factor 3 in ischemic penumbra region following transient middle cerebral artery occlusion and reperfusion injury

Song, Dae-Yong; Oh, Kyoung-Min; Yu, Ha-Nul; Park, Chae-Ri; Woo, Ran-Sook; Jung, Sung-Sam; Baik, Tai-Kyoung

doi:10.1016/j.neures.2011.05.002

Cited by 22 publications

(26 citation statements)

References 33 publications

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“…One highly important observation for genomic studies has been that the expression of many transcription factors that promote either neuronal death or neuroprotection change rapidly after stroke and post-ischemic outcome can be altered by modulating these transcription factors (Bernaudin et al, 2002; Collino et al, 2006; Iadecola et al, 1999; Kapadia et al, 2006; Satriotomo et al, 2006; Shih et al, 2005; Song et al, 2011; Tanaka et al, 2000a; Tanaka et al, 2000b; Tureyen et al, 2008; Tureyen et al, 2007; Venna et al, 2012). …”

Section: Stroke Alters Cerebral Protein-coding Gene Expressionmentioning

confidence: 99%

All’s well that transcribes well: Non-coding RNAs and post-stroke brain damage

Vemuganti

2013

Neurochemistry International

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The mammalian genome is replete with various classes of non-coding (nc) RNA genes. Many of them actively transcribe, and their relevance to CNS diseases is just beginning to be understood. CNS is one of the organs in the body that shows very high ncRNAs activity. Recent studies demonstrated that cerebral ischemia rapidly changes the expression profiles of different classes of ncRNAs: including microRNA, long noncoding RNA and piwi-interacting RNA. Several studies further showed that post-ischemic neuronal death and/or plasticity/regeneration can be altered by modulating specific microRNAs. These studies are of interest for therapeutic development as they may contribute to identifying new ncRNA targets that can be modulated to prevent secondary brain damage after stroke.

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Section: Stroke Alters Cerebral Protein-coding Gene Expressionmentioning

confidence: 99%

All’s well that transcribes well: Non-coding RNAs and post-stroke brain damage

Vemuganti

2013

Neurochemistry International

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“…Under normal conditions, ATF3 is expressed at minimal levels. However, ATF3 can be induced by various stress signals including ischemia 10 , ER stress 11 , endotoxins, and cytokines 12 . ATF3 is rapidly and preferentially induced during the early stage of the inflammatory response in organ IRI, such as in the kidney 13,14 and brain 15 .…”

Section: Introductionmentioning

confidence: 99%

Loss of ATF3 exacerbates liver damage through the activation of mTOR/p70S6K/ HIF-1α signaling pathway in liver inflammatory injury

et al. 2018

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Activating transcription factor 3 (ATF3) is a stress-induced transcription factor that plays important roles in regulating immune and metabolic homeostasis. Activation of the mechanistic target of rapamycin (mTOR) and hypoxia-inducible factor (HIF) transcription factors are crucial for the regulation of immune cell function. Here, we investigated the mechanism by which the ATF3/mTOR/HIF-1 axis regulates immune responses in a liver ischemia/reperfusion injury (IRI) model. Deletion of ATF3 exacerbated liver damage, as evidenced by increased levels of serum ALT, intrahepatic macrophage/neutrophil trafficking, hepatocellular apoptosis, and the upregulation of pro-inflammatory mediators. ATF3 deficiency promoted mTOR and p70S6K phosphorylation, activated high mobility group box 1 (HMGB1) and TLR4, inhibited prolyl-hydroxylase 1 (PHD1), and increased HIF-1α activity, leading to Foxp3 downregulation and RORγt and IL-17A upregulation in IRI livers. Blocking mTOR or p70S6K in ATF3 knockout (KO) mice or bone marrow-derived macrophages (BMMs) downregulated HMGB1, TLR4, and HIF-1α and upregulated PHD1, increasing Foxp3 and decreasing IL-17A levels in vitro. Silencing of HIF-1α in ATF3 KO mice ameliorated IRI-induced liver damage in parallel with the downregulation of IL-17A in ATF3-deficient mice. These findings demonstrated that ATF3 deficiency activated mTOR/p70S6K/HIF-1α signaling, which was crucial for the modulation of TLR4-driven inflammatory responses and T cell development. The present study provides potential therapeutic targets for the treatment of liver IRI followed by liver transplantation.

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“…Furthermore, neuronal apoptosis and necrosis in the penumbra can be viewed as primary causes of aggravated cerebral injury and functional impairment. Additionally, neuronal apoptosis can be exacerbated by the excessive formation of inflammatory reactions after an ischemic stroke, which has been demonstrated to be the one cause contributing to cerebral I/R injury2. Although several studies have been devoted to developing methods to reduce inflammatory reactions during ischemic cerebral injury, effective methods have not yet been established.…”

mentioning

confidence: 99%

Isoflurane preconditioning provides neuroprotection against stroke by regulating the expression of the TLR4 signalling pathway to alleviate microglial activation

Sun

Deng

Zhao

et al. 2015

Sci Rep

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Excessive microglial activation often contributes to inflammation-mediated neurotoxicity in the ischemic penumbra during the acute stage of ischemic stroke. Toll-like receptor 4 (TLR4) has been reported to induce microglial activation via the NF-κB pathway. Isoflurane preconditioning (IP) can provide neuroprotection and inhibit microglial activation. In this study, we investigated the roles of the TLR4 signalling pathway in IP to exert neuroprotection following ischemic stroke in vivo and in vitro. The results showed that 2% IP alleviated neurological deficits, reduced the infarct volume, attenuated apoptosis and weakened microglial activation in the ischemic penumbra. Furthermore, IP down-regulated the expression of HSP 60, TLR4 and MyD88 and up-regulated inhibitor of IκB-α expression compared with I/R group in vivo. In vitro, 2% IP and a specific inhibitor of TLR4, CLI-095, down-regulated the expression of TLR4, MyD88, IL-1β, TNF-α and Bax, and up-regulated IκB-α and Bcl-2 expression compared with OGD group. Moreover, IP and CLI-095 attenuated microglial activation-induced neuronal apoptosis, and overexpression of the TLR4 gene reversed the neuroprotective effects of IP. In conclusion, IP provided neuroprotection by regulating TLR4 expression directly, alleviating microglial activation and neuroinflammation. Thus, inhibiting the activation of microglial activation via TLR4 may be a new avenue for stroke treatment.

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Role of activating transcription factor 3 in ischemic penumbra region following transient middle cerebral artery occlusion and reperfusion injury

Cited by 22 publications

References 33 publications

All’s well that transcribes well: Non-coding RNAs and post-stroke brain damage

All’s well that transcribes well: Non-coding RNAs and post-stroke brain damage

Loss of ATF3 exacerbates liver damage through the activation of mTOR/p70S6K/ HIF-1α signaling pathway in liver inflammatory injury

Isoflurane preconditioning provides neuroprotection against stroke by regulating the expression of the TLR4 signalling pathway to alleviate microglial activation

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