Sirt3 Mediates the Inhibitory Effect of Adjudin on Astrocyte Activation and Glial Scar Formation following Ischemic Stroke

Yang, Xiao; Geng, Keyi; Zhang, Jinfan; Zhang, Yanshuang; Shao, Jiaxiang; Xia, Weiliang

doi:10.3389/fphar.2017.00943

Cited by 32 publications

(25 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SIRT3 reduced the production of superoxide dismutase and increased the migratory potential of microglia cells in vitro (Cao et al, 2019). Upregulation of SIRT3 in astrocytes also inhibited their inflammatory activation, highlighting the possibility of metabolic regulation by targeting epigenetics (Yang et al, 2017). Adjudin treatment promoted the functional recovery in ischemic mice by inhibiting the inflammatory activation of astrocytes through Sirt 3 upregulation (Yang et al, 2017).…”

Section: Modulation Of Glial Metabolism As a Therapeutic Strategymentioning

confidence: 98%

Metabolic Regulation of Glial Phenotypes: Implications in Neuron–Glia Interactions and Neurological Disorders

Afridi

Kim

Rahman

et al. 2020

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Glial cells are multifunctional, non-neuronal components of the central nervous system with diverse phenotypes that have gained much attention for their close involvement in neuroinflammation and neurodegenerative diseases. Glial phenotypes are primarily characterized by their structural and functional changes in response to various stimuli, which can be either neuroprotective or neurotoxic. The reliance of neurons on glial cells is essential to fulfill the energy demands of the brain for its proper functioning. Moreover, the glial cells perform distinct functions to regulate their own metabolic activities, as well as work in close conjunction with neurons through various secreted signaling or guidance molecules, thereby constituting a complex network of neuron-glial interactions in health and disease. The emerging evidence suggests that, in disease conditions, the metabolic alterations in the glial cells can induce structural and functional changes together with neuronal dysfunction indicating the importance of neuron-glia interactions in the pathophysiology of neurological disorders. This review covers the recent developments that implicate the regulation of glial phenotypic changes and its consequences on neuron-glia interactions in neurological disorders. Finally, we discuss the possibilities and challenges of targeting glial metabolism as a strategy to treat neurological disorders.

show abstract

Section: Modulation Of Glial Metabolism As a Therapeutic Strategymentioning

confidence: 98%

Metabolic Regulation of Glial Phenotypes: Implications in Neuron–Glia Interactions and Neurological Disorders

Afridi

Kim

Rahman

et al. 2020

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Previously, it was reported that the SIRT3-FOXO3a signaling pathway was involved in the inhibitory effect of Adjudin on astrocyte activation. 15 Therefore, we hypothesized that this pathway also played a significant role in the anticancer effect of Adjudin on SCLC cells. In our study, FOXO3a siRNA was used to transfect cells that had already overexpressed SIRT3.…”

Section: Adjudin Upregulated Foxo3a By Activating Sirt3mentioning

confidence: 99%

Adjudin synergizes with paclitaxel and inhibits cell growth and metastasis by regulating the sirtuin 3–Forkhead box O3a axis in human small‐cell lung cancer

Wang

Zeng

et al. 2019

Thoracic Cancer

Self Cite

View full text Add to dashboard Cite

Background Small‐cell lung cancer (SCLC), a malignant tumor, is usually widely metastatic when diagnosed. The lack of important therapeutic clinical advances makes it difficult to treat. Previous studies showed that Adjudin had anticancer effects in many other human cancers, and it was synergetic with cisplatin in non‐small cell lung cancer. However, the mechanism on SCLC was unclear. Methods We investigated the potential mechanism and effect of Adjudin on SCLC both in vitro and in vivo . Results An SCLC xenograft model showed that Adjudin inhibited tumor growth and was significantly synergetic with paclitaxel ( in vitro as well). Cell Counting Kit‐8 assays, flow cytometric analysis and western blotting showed that Adjudin effectively suppressed SCLC cell proliferation by inducing S phase arrest and caspase‐dependent apoptosis. Moreover, Transwell and scratch assays showed that Adjudin also effectively inhibited migration and invasion. Furthermore, Adjudin activated the sirtuin 3 (SIRT3)–Forkhead box O3a (FOXO3a) pathway. Downregulating SIRT3 or FOXO3a significantly attenuated Adjudin‐induced anticancer effects. Furthermore, higher expression of SIRT3 and FOXO3a were positively correlated, and both were associated with longer survival in lung cancer patients. Conclusion Overall, the present study is the first to show that Adjudin synergizes with paclitaxel and inhibits cell growth and metastasis by regulating the SIRT3–FOXO3a axis in SCLC; thus, Adjudin has great potential to be an anticancer agent.

show abstract

“…Another report found that SIRT3 was responsible for the neuroprotective effects of ketone treatment following cerebral ischemia ( Yin et al, 2015 ). SIRT3 was found to be involved in inhibiting astrocyte activation in a mouse MCAO model which decreased glial scarring ( Yang et al, 2017 ). It has been purposed that SIRT3 activity could be regulated by mitochondrial uncoupling protein 2 (UCP2) during cerebral ischemia-reperfusion injury by increasing the available NAD+/NADH ratio ( Su et al, 2017 ).…”

Section: Sirt3 Modulation After Strokementioning

confidence: 99%

SIRT3 Regulation Under Cellular Stress: Making Sense of the Ups and Downs

Marcus

Andrabi

2018

Front. Neurosci.

View full text Add to dashboard Cite

Sirtuin 3 (SIRT3) is an NAD+ dependent deacetylase that resides primarily in mitochondria and functions to maintain mitochondrial homeostasis under stress. SIRT3 expression has been observed to change under a number of different stresses in multiple tissues and model systems. Inconsistencies in the literature with regards to how and when SIRT3 protein levels change indicates that the mechanism of SIRT3 regulation is multi-faceted. Alterations in SIRT3 have been observed in experimental models of cellular stress, however, the effect these changes have on mitochondrial health remain unknown. Neurons are highly dependent on proper mitochondrial function for their survival. SIRT3 dynamics and function have been studied using models of genotoxic, metabolic, and oxidative stresses, although it remains unclear how SIRT3 is being regulated under these conditions. A closer look into SIRT3 regulation under stress conditions in various model systems will help incorporate the many SIRT3 regulatory mechanisms at play in disease states. In this review, we describe the observations that have been made about SIRT3 protein modulation under basic stress conditions. We then point out consistencies and contradictions in these observations and what they mean. Lastly, we present the observations made in the complicated neuronal stress of stroke. We hope that this review will help consolidate the ambiguous SIRT3 literature and provide a framework for investigation of SIRT3 regulation during stress response.

show abstract

Sirt3 Mediates the Inhibitory Effect of Adjudin on Astrocyte Activation and Glial Scar Formation following Ischemic Stroke

Cited by 32 publications

References 37 publications

Metabolic Regulation of Glial Phenotypes: Implications in Neuron–Glia Interactions and Neurological Disorders

Metabolic Regulation of Glial Phenotypes: Implications in Neuron–Glia Interactions and Neurological Disorders

Adjudin synergizes with paclitaxel and inhibits cell growth and metastasis by regulating the sirtuin 3–Forkhead box O3a axis in human small‐cell lung cancer

SIRT3 Regulation Under Cellular Stress: Making Sense of the Ups and Downs

Contact Info

Product

Resources

About