Sirtuin 3 regulates Foxo3a-mediated antioxidant pathway in microglia

Rangarajan, Parakalan; Karthikeyan, A.; Lu, Jia; Ling, Eng‐Ang; Dheen, S. Thameem

doi:10.1016/j.neuroscience.2015.10.048

Cited by 118 publications

(87 citation statements)

References 26 publications

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“…SIRT3 is also reported to be a nuclear NAD + ‐dependent histone deacetylase targeting histone 3 lysine 9 (H3K9) and histone 4 lysine 16 (H4K16) during cellular stress conditions . SIRT3 regulates a wide range of important biological functions including metabolic control, neuroprotection, cardiovascular diseases, aging, and cancer, mainly through its deacetylase activity. However, its role in HBV replication remains unexplored.…”

mentioning

confidence: 99%

SIRT3 restricts hepatitis B virus transcription and replication through epigenetic regulation of covalently closed circular DNA involving suppressor of variegation 3‐9 homolog 1 and SET domain containing 1A histone methyltransferases

Ren

Cheng

et al. 2018

Hepatology

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mentioning

confidence: 99%

SIRT3 restricts hepatitis B virus transcription and replication through epigenetic regulation of covalently closed circular DNA involving suppressor of variegation 3‐9 homolog 1 and SET domain containing 1A histone methyltransferases

Ren

Cheng

et al. 2018

Hepatology

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“…FoxO3a also plays a key role in ROS production (27) and regulation of FoxO3a by MAPK signaling in response to oxidative stress (28). In addition, FoxO3a mediates activation of antioxidant genes, such as SOD and CAT (29). A recent study showed that saponins activated FoxO3a, and nuclear factor-erythroid 2-related factor 2 (Nrf2) increased the expression and function of multiple antioxidants, at least partly contributing to the protection of D-galactose-induced aging in rats (30).…”

Section: Discussionmentioning

confidence: 99%

FoxO3a plays a key role in the protective effects of pomegranate peel extract against amikacin-induced ototoxicity

Liu

Zhang

Sun

et al. 2017

International Journal of Molecular Medicine

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The use of amikacin (AMK) in present treatment strategies results in severe ototoxicity; however, the underlying molecular mechanisms of this toxicity remain unclear. In this study, we investigated the effectiveness of orally administered pomegranate peel extract (PPE), a strong antioxidant, as a protective agent against AMK-induced ototoxicity. To this end, PPE was orally administered to adult BALB/c mice for 5 days, and the mice were then concurrently treated with AMK (500 mg/kg/day for 15 consecutive days). Auditory threshold shifts induced by AMK were significantly attenuated. The results of immunohistochemical staining and western blot analysis revealed that PPE exerted its protective effects by by downregulating the phosphorylation of Forkhead box O3a (FoxO3a), an important transcription factor which is involved in the responses to oxidative stress. The results also showed that PPE treatment inhibited mitogen-activated protein kinase phosphorylation, prevented the activation of pro-apoptotic protein caspase-3, decreased the levels of apoptosis-inducing Bax protein, and increased the levels of the anti-apoptotic mediator, Bcl-2, induced by AMK in the mouse cochlea. Taken together, our experimental findings suggest that phosphorylated FoxO3a mediates AMK-induced apoptosis in BALB/c mice cochlea. PPE effectively attenuated oxidative stress and ototoxicity by regulating FoxO3a, and may thus prove to be beneficial in protecting auditory cells from ototoxic drugs.

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“…SIRT3 has been shown to directly deacetylate and stimulate manganese superoxide dismutase (MnSOD) activity, which is the principle ROS scavenger in the mitochondria [20]. In addition, SIRT3 could induce expression of MnSOD, catalase, and isocitrate dehydrogenase (IDH2) by deacetylating FOXO3a transcription factor, triggering its translocation into the nucleus and transcription of these antioxidant enzymes [20,25,41,42].…”

Section: Changes In Sirtuin 3 Expression In Carcinogenesismentioning

confidence: 99%

Changes in the Expression and the Role of Sirtuin 3 in Cancer Cells and in Cardiovascular Health and Disease

Özden¹,

Tural²

2018

Gene Expression and Regulation in Mammalian Cells - Transcription Toward the Establishment of Novel Therapeutics

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Sirtuin 3, an NAD + -dependent deacetylase, whose expression is considered a marker in life extension, is downregulated with age and in various diseases. Sirtuin 3 is predominantly localized to the mitochondria and considered a fidelity protein for the integrity and function of this organelle. Some studies report its localization in the nucleus to regulate the expression of stress response-related genes and that reduced expression of SIRT3 produces a cellular milieu permissive for human pathologies. Since the expression and activity of Sirtuin 3 are important for the regulation of antioxidant defense, metabolism, and apoptosis initiation, the expression of SIRT3 is also important in the context of ageassociated illnesses. A variety of small molecules are being developed to modulate the expression or activity of Sirtuin 3 and are potentially a valuable strategy to change mitochondrial acetylome to treat several diseases. The AMPK-PGC1α-SIRT3 axis plays a critical role in preserving mitochondrial biogenesis and function. Here, we summarize how changes in Sirtuin 3 expression are regulated in cancer and dysfunctions in cardiovascular diseases. The potential therapeutic strategies by targeting Sirtuin 3 expression to improve mitochondrial function in cancer and cardiovascular diseases are summarized.

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Sirtuin 3 regulates Foxo3a-mediated antioxidant pathway in microglia

Cited by 118 publications

References 26 publications

SIRT3 restricts hepatitis B virus transcription and replication through epigenetic regulation of covalently closed circular DNA involving suppressor of variegation 3‐9 homolog 1 and SET domain containing 1A histone methyltransferases

SIRT3 restricts hepatitis B virus transcription and replication through epigenetic regulation of covalently closed circular DNA involving suppressor of variegation 3‐9 homolog 1 and SET domain containing 1A histone methyltransferases

FoxO3a plays a key role in the protective effects of pomegranate peel extract against amikacin-induced ototoxicity

Changes in the Expression and the Role of Sirtuin 3 in Cancer Cells and in Cardiovascular Health and Disease

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