6-gingerol protects nucleus pulposus-derived mesenchymal stem cells from oxidative injury by activating autophagy

Li, Nan; Wang, Feng; Liu, Yang; Wu, Zhong; Feng, Xinmin; Liu, Junjian; Zhang, Liang

doi:10.4252/wjsc.v12.i12.1603

Cited by 17 publications

(19 citation statements)

References 49 publications

(21 reference statements)

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“…An appropriate concentration of H 2 O 2 to induce oxidative stress damage in NPMSCs was confirmed in our previous study[ 20 ]. The viability effects of UA and the PGC-1α inhibitor SR-18292 on NPMSCs were analyzed using a CCK-8 assay.…”

Section: Resultssupporting

confidence: 58%

“…The inflammation, apoptosis and senescence of NP cells and the apoptosis and senescence of NPMSCs are important pathological models for exploring IDD, which can all be induced by H 2 O 2 treatment[ 23 - 26 ]. In our previous study, we confirmed that H 2 O 2 treatment could decrease the viability of NPMSCs in a dose- and concentration-dependent manner, and a concentration of 80 μM for 6 h could be used as a suitable concentration in vitro [ 20 ]. Cell senescence often exhibits the characteristics of irreversible cell cycle arrest, loss of proliferation capacity and reduced cell anabolic ability.…”

Section: Discussionmentioning

confidence: 79%

“…H 2 O 2 is commonly used to induce oxidative damage in mechanistic studies of IDD[ 20 , 22 ]. The inflammation, apoptosis and senescence of NP cells and the apoptosis and senescence of NPMSCs are important pathological models for exploring IDD, which can all be induced by H 2 O 2 treatment[ 23 - 26 ].…”

Section: Discussionmentioning

confidence: 99%

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Urolithin a alleviates oxidative stress-induced senescence in nucleus pulposus-derived mesenchymal stem cells through SIRT1/PGC-1α pathway

Shi¹,

Wang²,

Wang³

et al. 2021

WJSC

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BACKGROUND In degenerative intervertebral disc (IVD), an unfavorable IVD environment leads to increased senescence of nucleus pulposus (NP)-derived mesenchymal stem cells (NPMSCs) and the inability to complete the differentiation from NPMSCs to NP cells, leading to further aggravation of IVD degeneration (IDD). Urolithin A (UA) has been proven to have obvious effects in delaying cell senescence and resisting oxidative stress. AIM To explore whether UA can alleviate NPMSCs senescence and to elucidate the underlying mechanism. METHODS In vitro , we harvested NPMSCs from rat tails, and divided NPMSCs into four groups: the control group, H 2 O 2 group, H 2 O 2 + UA group, and H 2 O 2 + UA + SR-18292 group. Senescence-associated β-Galactosidase (SA-β-Gal) activity, cell cycle, cell proliferation ability, and the expression of senescence-related and silent information regulator of transcription 1/PPAR gamma coactivator-1α (SIRT1/ PGC-1α) pathway-related proteins and mRNA were used to evaluate the protective effects of UA. In vivo , an animal model of IDD was constructed, and X-rays, magnetic resonance imaging, and histological analysis were used to assess whether UA could alleviate IDD in vivo . RESULTS We found that H 2 O 2 can cause NPMSCs senescence changes, such as cell cycle arrest, reduced cell proliferation ability, increased SA-β-Gal activity, and increased expression of senescence-related proteins and mRNA. After UA pretreatment, the abovementioned senescence indicators were significantly alleviated. To further demonstrate the mechanism of UA, we evaluated the mitochondrial membrane potential and the SIRT1/PGC-1α pathway that regulates mitochondrial function. UA protected mitochondrial function and delayed NPMSCs senescence by activating the SIRT1/PGC-1α pathway. In vivo , we found that UA treatment alleviated an animal model of IDD by assessing the disc height index, Pfirrmann grade and the histological score. CONCLUSION In summary, UA could activate the SIRT1/PGC-1α signaling pathway to protect mitochondrial function and alleviate cell senescence and IDD in vivo and vitro .

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Section: Resultssupporting

confidence: 58%

Section: Discussionmentioning

confidence: 79%

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Urolithin a alleviates oxidative stress-induced senescence in nucleus pulposus-derived mesenchymal stem cells through SIRT1/PGC-1α pathway

Shi¹,

Wang²,

Wang³

et al. 2021

WJSC

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“…The results showed that 1,25(OH) 2 D 3 showed no cytotoxic effect on cell viability at a concentration of 10 −8 M to 10 −12 M for the different exposure times (0, 12, 24, and 48 h) ( Figure 2(a) ); 10 −10 M of 1,25(OH) 2 D 3 was chosen for the subsequent experiments. Additionally, cell proliferation was appropriately inhibited when treated with 100 μ M H 2 O 2 for 6 h, which was the same result as our previous study [ 24 , 33 ] ( Figure 2(b) ). Therefore, this condition was used to induce oxidative stress damage in NPMSCs in the following experiments.…”

Section: Resultssupporting

confidence: 90%

1,25(OH)2D3 Mitigates Oxidative Stress-Induced Damage to Nucleus Pulposus-Derived Mesenchymal Stem Cells through PI3K/Akt Pathway

Wang

Zhu

Shi

et al. 2022

Oxidative Medicine and Cellular Longevity

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Intervertebral disc degeneration (IVDD) is one of the main causes of low back pain. The local environment of the degenerated intervertebral disc (IVD) increases oxidative stress and apoptosis of endogenous nucleus pulposus-derived mesenchymal stem cells (NPMSCs) and weakens its ability of endogenous repair ability in degenerated IVDs. A suitable concentration of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) has been certified to reduce oxidative stress and cell apoptosis. The current study investigated the protective effect and potential mechanism of 1,25(OH)2D3 against oxidative stress-induced damage to NPMSCs. The present results showed that 1,25(OH)2D3 showed a significant protective effect on NPMSCs at a concentration of 10-10 M for 24 h. Protective effects of 1,25(OH)2D3 were also exhibited against H2O2-induced NPMSC senescence, mitochondrial dysfunction, and reduced mitochondrial membrane potential. The Annexin V/PI apoptosis detection assay, TUNEL assay, immunofluorescence, western blot, and real-time quantitative polymerase chain reaction assay showed that pretreatment with 1,25(OH)2D3 could alleviate H2O2-induced NPMSC apoptosis, including the apoptosis rate and the expression of proapoptotic-related (Caspase-3 and Bax) and antiapoptotic-related (Bcl-2) proteins. The intracellular expression of p-Akt increased after pretreatment with 1,25(OH)2D3. However, these protective effects of 1,25(OH)2D3 were significantly decreased after the PI3K/Akt pathway was inhibited by the LY294002 treatment. In vivo, X-ray, MRI, and histological analyses showed that 1,25(OH)2D3 treatment relieved the degree of IVDD in Sprague–Dawley rat disc puncture models. In summary, 1,25(OH)2D3 efficiently attenuated oxidative stress-induced NPMSC apoptosis and mitochondrial dysfunction via PI3K/Akt pathway and is a promising candidate treatment for the repair of IVDD.

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“…Studies have shown that excessive apoptosis of NP cells plays a crucial role in the development of IDD (Guo et al, 2018;Yu et al, 2018). In addition, previous studies have shown that oxidative stress participates in the apoptosis process of NP cells (Nan et al, 2020). Nevertheless, the underlying mechanisms of apoptosis induced by oxidative stress have not been fully clarified.…”

Section: Discussionmentioning

confidence: 99%

CRISPR/dCas9-Mediated Parkin Inhibition Impairs Mitophagy and Aggravates Apoptosis of Rat Nucleus Pulposus Cells Under Oxidative Stress

Lan

Zheng

et al. 2021

Front. Mol. Biosci.

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ObjectiveThe aim of this study is to explore the role of Parkin in intervertebral disk degeneration (IDD) and its mitophagy regulation mechanism.Study design and methodsRat nucleus pulposus (NP) cells were stimulated with hydrogen peroxide (H2O2) to a mimic pathological condition. Apoptosis and mitophagy were assessed by Western blot, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and immunofluorescence staining. The CRISPR–dCas9–KRAB system was used to silence the expression of Parkin.ResultIn this study, we found that Parkin was downregulated in rat NP cells under oxidative stress. In addition, treatment with H2O2 resulted in mitochondrial dysfunction, autophagy inhibition, and a significant increase in the rate of apoptosis of NP cells. Meanwhile, mitophagy inhibition enhanced H2O2-induced apoptosis. Furthermore, repression of Parkin significantly attenuated mitophagy and exacerbated apoptosis.ConclusionThese results suggested that Parkin may play a protective role in alleviating the apoptosis of NP cells via mitophagy, and that targeting Parkin may provide a promising therapeutic strategy for the prevention of IDD.

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6-gingerol protects nucleus pulposus-derived mesenchymal stem cells from oxidative injury by activating autophagy

Cited by 17 publications

References 49 publications

Urolithin a alleviates oxidative stress-induced senescence in nucleus pulposus-derived mesenchymal stem cells through SIRT1/PGC-1α pathway

Urolithin a alleviates oxidative stress-induced senescence in nucleus pulposus-derived mesenchymal stem cells through SIRT1/PGC-1α pathway

1,25(OH)2D3 Mitigates Oxidative Stress-Induced Damage to Nucleus Pulposus-Derived Mesenchymal Stem Cells through PI3K/Akt Pathway

CRISPR/dCas9-Mediated Parkin Inhibition Impairs Mitophagy and Aggravates Apoptosis of Rat Nucleus Pulposus Cells Under Oxidative Stress

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