Sirt1 Promotes Axonogenesis by Deacetylation of Akt and Inactivation of GSK3

Li, Xiaohong; Chen, Chong; Tu, Yue; Sun, Haitao; Zhao, Ming; Cheng, Shixiang; Qu, Yang; Zhang, Sai

doi:10.1007/s12035-013-8437-3

Cited by 110 publications

(94 citation statements)

References 36 publications

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“…S5B), suggesting that SIRT1 has the ability to promote axon growth. In support of this, previous studies have shown that overexpression of SIRT1 can drastically promote axon growth of embryonic cortical neurons (Guo et al 2011;Li et al 2013), which do not up-regulate SIRT1 automatically in culture.…”

Section: Sirt1 Controls Sensory Axon Regeneration In Vitro and In Vivosupporting

confidence: 52%

“…However, we showed that in embryonic cortical neurons, where the expressions of endogenous miR-138 and SIRT1 do not change, inhibiting miR-138 led to increased axon growth. Similarly, two previous studies have also shown that overexpression of SIRT1 in cortical neurons was sufficient to promote axon growth (Guo et al 2011;Li et al 2013). Thus, manipulation of miR-138 and SIRT1 expression is an effective approach to promote axon growth.…”

Section: Discussionmentioning

confidence: 54%

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MicroRNA-138 and SIRT1 form a mutual negative feedback loop to regulate mammalian axon regeneration

et al. 2013

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Regulated gene expression determines the intrinsic ability of neurons to extend axons, and loss of such ability is the major reason for the failed axon regeneration in the mature mammalian CNS. MicroRNAs and histone modifications are key epigenetic regulators of gene expression, but their roles in mammalian axon regeneration are not well explored. Here we report microRNA-138 (miR-138) as a novel suppressor of axon regeneration and show that SIRT1, the NAD-dependent histone deacetylase, is the functional target of miR-138. Importantly, we provide the first evidence that miR-138 and SIRT1 regulate mammalian axon regeneration in vivo. Moreover, we found that SIRT1 also acts as a transcriptional repressor to suppress the expression of miR-138 in adult sensory neurons in response to peripheral nerve injury. Therefore, miR-138 and SIRT1 form a mutual negative feedback regulatory loop, which provides a novel mechanism for controlling intrinsic axon regeneration ability.

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Section: Sirt1 Controls Sensory Axon Regeneration In Vitro and In Vivosupporting

confidence: 52%

Section: Discussionmentioning

confidence: 54%

MicroRNA-138 and SIRT1 form a mutual negative feedback loop to regulate mammalian axon regeneration

et al. 2013

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“…In sepsis, SIRT1 may promote the termination of the NF-κB-dependent transcription by its deacetylation effect of p65 and thus play a role in sepsis protection [6,39]. Additionally, SIRT1 directly or indirectly regulates the AKT pathway, [40,41]. Recent studies showed that SIRT1 is regulated by several mi-RNAs including miR-34a, miR-181, miR-217, etc.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-138 Aggravates Inflammatory Responses of Macrophages by Targeting SIRT1 and Regulating the NF-κB and AKT Pathways

Bai

Zhang

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: With increased understanding of sepsis, mortality is decreasing. However, there is still a lack of effective therapeutic strategy. The inflammatory response of macrophages is critical during sepsis. Methods: Macrophages were stimulated with LPS. Western blotting and qRT-PCR were used to detect inflammatory responses. Then, the inhibitor of microRNA-138 was transfected and Western blotting, qRT-PCR, H&E staining and ELISA were used to verify the role of microRNA-138 in inflammation. Then target gene prediction databases were used to predict the potential target of microRNA-138. Both animal and cell models under LPS challenges were established to verify the regulation of SIRT1 and microRNA-138 during inflammation. Results: The present study showed that microRNA-138 was increased in macrophages stimulated with LPS. Additionally, the NF-κB and AKT pathways were both activated. The pre-treatment of microRNA-138 inhibitor decreased inflammatory factors, downregulated the NF-κB pathway, activated the AKT pathway and protected against organ damage in mice challenged with LPS. SIRT1 was demonstrated as a potential target of microRNA-138In macrophages stimulated with LPS, the inhibition effect of microRNA-138 inhibitor on inflammation was lost by SIRT1 siRNA pre-treatment. In the animal model, the protective effect of microRNA-138 antagomir disappeared in SIRT1 knockout mice. Conclusion: We demonstrated that miR-138 participated in the inflammatory process by inhibiting SIRT1 and activating the NF-κB pathway.

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“…In supporting this, Wu et al (2011) found that consecutive activation of AKT by Ser473 phosphorylation promotes its rapid degradation by a polyubiquitination-dependent proteosomal pathway, thereby turning off the AKT signaling . Given that SIRT1 promotes AKT phosphorylation through deacetylation (Horio, 2012;Li et al, 2013), SRT1720-induced SIRT1 activity might stimulate sustained activation of AKT, which in turn leads to degradation of AKT and reduction of total AKT levels.…”

Section: Discussionmentioning

confidence: 99%

Activation of Sirtuin-1 Promotes Renal Fibroblast Activation and Aggravates Renal Fibrogenesis

Ponnusamy

Zhuang

Zhou

et al. 2015

J Pharmacol Exp Ther

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Although activation of sirtuin-1 (SIRT1) has been shown to protect the kidney from acute injury, its role in renal fibrosis remains controversial since both inhibition and activation of SIRT1 have been reported to attenuate renal fibrosis. To resolve this conflict, we further examined the effect of SIRT1 activators on the activation of renal interstitial fibroblasts and development of renal fibrosis in vivo and in vitro. In a murine model of renal fibrosis induced by unilateral ureteral obstruction, administration , another SIRT1 activator, also resulted in enhanced expression of a-SMA and fibronectin. Mechanistic studies showed that augmentation of renal fibrogenesis by SRT1720 is associated with elevated phosphorylation of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor b (PDGFRb). SRT1720 treatment also increased the phosphorylation of signal transducer and activator of transcription 3 and protein kinase B in the fibrotic kidney and NRK-49F cells. However, SRT1720 treatment did not affect expression of proliferating cell nuclear protein, a proliferation marker and activation of extracellular signal regulated kinase 1/2 in vitro and in vivo. These results indicate that SIRT1-activating compounds can provoke renal fibrogenesis through a mechanism involved in the activation of EGFR and PDGFR signaling pathways and suggest that long-term use of SIRT1 activators risks the development and progression of chronic kidney disease.

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Sirt1 Promotes Axonogenesis by Deacetylation of Akt and Inactivation of GSK3

Cited by 110 publications

References 36 publications

MicroRNA-138 and SIRT1 form a mutual negative feedback loop to regulate mammalian axon regeneration

MicroRNA-138 and SIRT1 form a mutual negative feedback loop to regulate mammalian axon regeneration

MicroRNA-138 Aggravates Inflammatory Responses of Macrophages by Targeting SIRT1 and Regulating the NF-κB and AKT Pathways

Activation of Sirtuin-1 Promotes Renal Fibroblast Activation and Aggravates Renal Fibrogenesis

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