Resveratrol Attenuates CoCl2-Induced Cochlear Hair Cell Damage through Upregulation of Sirtuin1 and NF-κB Deacetylation

Wang, Ping; Du, Bin; Yin, Wen; Wang, Xinrui; Zhu, Wei

doi:10.1371/journal.pone.0080854

Cited by 14 publications

(8 citation statements)

References 37 publications

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“…Moreover, other studies have reported the beneficial effect of resveratrol on hair cells (Bonabi, Caelers, Monge, Huber, & Bodmer, 2008;Wang, Du, Yin, Wang, & Zhu, 2013;Xiong et al, 2015) In this study, we examined the role of OVOL1 during osteoblast differentiation and confirmed that resveratrol-induced OVOL1 expression mediates osteoblast differentiation. Here, we suggest that OVOL1 is necessary for osteoblast differentiation as it is involved in the induction of BMP2 in preosteoblastic MC3T3-E1 cells.…”

Section: Introductionsupporting

confidence: 74%

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OVO homologue‐like 1 promotes osteoblast differentiation through BMP2 expression

Min

Sung

Kim

et al. 2018

Journal Cellular Physiology

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OVO homologue‐like 1 (OVOL1) encodes a C2H2 zinc finger protein and is an evolutionarily conserved gene in mammals. The OVOL1 expression is required for development. However, the function of OVOL1 in bone metabolism remains unreported. Here, we show for the first time the role of OVOL1 in osteoblast differentiation. To determine the role of OVOL1 in osteogenic differentiation, we analyzed OVOL1 expression in the preosteoblastic cell line. OVOL1 messenger RNA expression was induced during osteoblast differentiation. In addition, OVOL1 overexpression enhanced the expression of osteogenic genes including bone morphogenetic protein 2 (BMP2), the inhibitor of DNA binding 1 (Id1), distal‐less homeobox 5 (Dlx5), runt‐related transcription factor 2 (Runx2), osteocalcin (OC), and alkaline phosphatase (ALP). Moreover, mineralization of the extracellular matrix was increased by OVOL1 overexpression in MC3T3‐E1 cells. Furthermore, knockdown of the OVOL1 experiment demonstrated that OVOL1 is required for osteoblast differentiation. Collectively, these results suggest that OVOL1 function as an important regulator of osteoblast differentiation by inducing BMP2 expression in MC3T3‐E1 cells.

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Section: Introductionsupporting

confidence: 74%

“…It has been reported that resveratrol enhances osteoblast differentiation through several signal pathway (Su et al, ; Tseng et al, ). In addition, resveratrol attenuates hair cell damage by activating Sirtuin1 (Wang et al, ). Also, resveratrol prevents cochlear hair cell apoptosis via miR‐34a/SIRT1/p53 signaling (Xiong et al, ).…”

Section: Discussionmentioning

confidence: 99%

OVO homologue‐like 1 promotes osteoblast differentiation through BMP2 expression

Min

Sung

Kim

et al. 2018

Journal Cellular Physiology

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“…Moreover, both moracin O and P significantly protected HaCaT cells against TRAIL-induced cytotoxicity, possibly through the inhibition of apoptosis. Considering that NF-κB-mediated inflammation has been implicated in the regulation of cellular damage by balancing anti-and pro-apoptotic protein expression (31)(32)(33)(34), moracin O and P may protect against HaCaT cell damage through their anti-inflammatory activity by targeting the NF-κB pathway. In the present study, moracin O and P as novel anti-inflammatory compounds inhibiting cellular damage induced by NF-κB activation.…”

Section: Discussionmentioning

confidence: 99%

Anti‑inflammatory compounds moracin O and P from Morus alba Linn. (Sohakuhi) target the NF‑κB pathway

Hardianti

Umeyama

et al. 2020

Mol Med Rep

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Accumulating evidence suggests that inflammation is linked to multiple pathological processes and induces cellular and molecular damage through the activation of inflammatory signaling pathways, including the NF-κB pathway. The aim of the present study was to identify natural anti-inflammatory products that can target NF-κB activity, in order to establish a novel therapeutic approach for inflammatory diseases. Using a 4T1 breast cancer cell line that expresses the firefly luciferase gene under the control of an NF-κB response element, 112 natural products were tested for their anti-inflammatory properties. Sohakuhi (Morus alba Linn. bark) extract was observed to strongly suppress NF-κB activity without affecting cell viability. To further examine the anti-inflammatory effect of Sohakuhi, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cellular damage of human HaCaT keratinocytes was evaluated. While TRAIL triggered the phosphorylation of the p65 subunit of NF-κB, leading to cellular damage in HaCaT cells, treatment with Sohakuhi extract protected HaCaT cells against TRAIL-induced cellular damage. Moreover, Sohakuhi treatment also upregulated the anti-apoptotic proteins Bcl-xL and Bcl-2. Importantly, through chemical fractionation of Sohakuhi extract, moracin O and P were confirmed to mediate its anti-inflammatory effects. Collectively, the present results indicated that Sohakuhi and moracin may represent potential candidates for the development of novel anti-inflammatory drugs.

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“…A number of studies have shown resveratrol to be protective against various forms of HC damage including cisplatin ( Yumusakhuylu et al, 2012 ) and noise ( Hanci et al, 2016 ) in vivo , as well as gentamicin in vitro treatment ( Bonabi et al, 2008 ). In addition to its antioxidant properties, resveratrol has been shown to activate sirtuin-1 and to de-acetylate NFκB, and these properties have been implicated in the protection of HCs from anoxic damage ( Wang et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

An Antioxidant Screen Identifies Candidates for Protection of Cochlear Hair Cells from Gentamicin Toxicity

Noack

Pak

Jalota

et al. 2017

Front. Cell. Neurosci.

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Reactive oxygen species are important elements in ototoxic damage to hair cells (HCs), appearing early in the damage process. Higher levels of natural antioxidants are positively correlated with resistance to ototoxins and many studies have shown that exogenous antioxidants can protect HCs from damage. While a very wide variety of antioxidants with different characteristics and intracellular targets exist, most ototoxicity studies have focused upon one or a few well-characterized compounds. Relatively little research has attempted to determine the comparative efficacy of large variety of different antioxidants. This has been in part due to the lack of translation between cell culture and in vivo measures of efficacy. To circumvent this limitation, we used an in vitro assay based on micro-explants from the basal and middle turns of the neonatal mouse organ of Corti to screen a commercial redox library of diverse antioxidant compounds for their ability to protect mammalian HCs from a high dose of the ototoxic antibiotic gentamicin. The library included several antioxidants that have previously been studied as potential treatments for HC damage, as well as many antioxidants that have never been applied to ototoxicity. The micro-explants were treated with 200 μM gentamicin alone, gentamicin plus one of three dosages of a redox compound, the highest dosage of compound alone, or were untreated. HC counts were determined before the gentamicin insult and at 1, 2, and 3 days afterward to evaluate the HC survival. From a total of 81 antioxidant compounds, 13 exhibited significant protection of HCs. These included members of a variety of antioxidant classes with several novel antioxidants, not previously tested on HCs, appearing to alleviate the damaging gentamicin effect. Some compounds previously shown to be protective of HCs were correspondingly protective in this in vitro screen, while others were not. Finally, one of the three pro-oxidant compounds included in the library as well as six antioxidants exhibited evidence of toxicity in the absence of gentamicin. The results demonstrate the wide variability in the ability of antioxidants to protect HCs from high-dose gentamicin damage, and identify promising candidate leads for further study as potential drug targets.Highlights• A medium-throughput assay based on micro-explants of the organ of Corti was developed to screen mammalian cochlear hair cells for protection from damage by ototoxins.• Eighty one antioxidants and 3 pro-oxidants were evaluated for hair cell protection from high-dose gentamicin.• Thirteen antioxidants were significantly protective, while 6 proved to be damaging.• The use of a common assay permitted an evaluation of the relative capacity of different antioxidants for the protection of hair cells.

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Resveratrol Attenuates CoCl2-Induced Cochlear Hair Cell Damage through Upregulation of Sirtuin1 and NF-κB Deacetylation

Cited by 14 publications

References 37 publications

OVO homologue‐like 1 promotes osteoblast differentiation through BMP2 expression

OVO homologue‐like 1 promotes osteoblast differentiation through BMP2 expression

Anti‑inflammatory compounds moracin O and P from Morus alba Linn. (Sohakuhi) target the NF‑κB pathway

An Antioxidant Screen Identifies Candidates for Protection of Cochlear Hair Cells from Gentamicin Toxicity

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