Reactive oxygen species-mediated mitochondrial dysfunction plays a critical role in high glucose-induced nucleus pulposus cell injury

Yang, Lianjun; Zhu, Lixin; Dong, Wei-Ren; Cao, Yanlin; Rong, Zijie; Zhang, Zanjie; Wu, Guofeng

doi:10.1007/s00264-013-2144-6

Cited by 14 publications

(11 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the in vivo study, we demonstrated that Sal activated the AMPK/mTOR signalling pathway to promote autophagic activity. In our in vitro study, we found that compound C‐mediated inhibition of AMPK phosphorylation abrogated the effects of Sal. These findings indicated that the upstream factor of the mTOR receptor, AMPK, may be an essential target in inflammation‐induced apoptosis and may mediate the protective effects of Sal in microglia (Fig.…”

Section: Discussionmentioning

confidence: 66%

Salidroside attenuates neuroinflammation and improves functional recovery after spinal cord injury through microglia polarization regulation

Wang

Lou

et al. 2017

J Cellular Molecular Medi

140

View full text Add to dashboard Cite

Spinal cord injury (SCI) is a severe neurological disease; however, few drugs have been proved to treat SCI effectively. Neuroinflammation is the major pathogenesis of SCI secondary injury and considered to be the therapeutic target of SCI. Salidroside (Sal) has been reported to exert anti‐inflammatory effects in airway, adipose and myocardial tissue; however, the role of Sal in SCI therapeutics has not been clarified. In this study, we showed that Sal could improve the functional recovery of spinal cord in rats as revealed by increased BBB locomotor rating scale, angle of incline, and decreased cavity of spinal cord injury and apoptosis of neurons in vivo. Immunofluorescence double staining of microglia marker and M1/M2 marker demonstrated that Sal could suppress M1 microglia polarization and activate M2 microglia polarization in vivo. To verify how Sal exerts its effects on microglia polarization and neuron protection, we performed the mechanism study in vitro in microglia cell line BV‐2 and neuron cell line PC12. The results showed that Sal prevents apoptosis of PC12 cells in coculture with LPS‐induced M1 BV‐2 microglia, also the inflammatory secretion phenotype of M1 BV‐2 microglia was suppressed by Sal, and further studies demonstrated that autophagic flux regulation through AMPK/mTOR pathway was involved in Sal regulated microglia polarization after SCI. Overall, our study illustrated that Sal could promote spinal cord injury functional recovery in rats, and the mechanism may relate to its microglia polarization modulation through AMPK‐/mTOR‐mediated autophagic flux stimulation.

show abstract

Section: Discussionmentioning

confidence: 66%

Salidroside attenuates neuroinflammation and improves functional recovery after spinal cord injury through microglia polarization regulation

Wang

Lou

et al. 2017

J Cellular Molecular Medi

140

View full text Add to dashboard Cite

show abstract

“…Recently, studies have verified the presence of oxidative stress and increased concentrations of oxidation products in degenerated discs . Additionally, oxidative stress and subsequent mitochondrial dysfunction participate in the intrinsic pathway of cellular apoptosis, which have been confirmed in NP cell death and IDD induced by various risk factors . Moreover, mitochondrial dysfunction induced by ROS can further enhance the production of ROS, leading to a feed‐forward vicious cycle between mitochondria and ROS that causes sustained oxidative damage .…”

Section: Introductionmentioning

confidence: 94%

The mitochondria‐targeted anti‐oxidant MitoQ protects against intervertebral disc degeneration by ameliorating mitochondrial dysfunction and redox imbalance

et al. 2020

View full text Add to dashboard Cite

Objective Mitochondrial dysfunction, oxidative stress and nucleus pulposus (NP) cell apoptosis are important contributors to the development and pathogenesis of intervertebral disc degeneration (IDD). Here, we comprehensively evaluated the effects of mitochondrial dynamics, mitophagic flux and Nrf2 signalling on the mitochondrial quality control, ROS production and NP cell survival in in vitro and ex vivo compression models of IDD and explored the effects of the mitochondria‐targeted anti‐oxidant MitoQ and its mechanism. Material and methods Human NP cells were exposed to mechanical compression to mimic pathological conditions. Results Compression promoted oxidative stress, mitochondrial dysfunction and NP cell apoptosis. Mechanistically, compression disrupted the mitochondrial fission/fusion balance, inducing fatal fission. Concomitantly, PINK1/Parkin‐mediated mitophagy was activated, whereas mitophagic flux was blocked. Nrf2 anti‐oxidant pathway was insufficiently activated. These caused the damaged mitochondria accumulation and persistent oxidative damage. Moreover, MitoQ restored the mitochondrial dynamics balance, alleviated the impairment of mitophagosome‐lysosome fusion and lysosomal function and enhanced the Nrf2 activity. Consequently, damaged mitochondria were eliminated, redox balance was improved, and cell survival increased. Additionally, MitoQ alleviated IDD in an ex vivo rat compression model. Conclusions These findings suggest that comodulation of mitochondrial dynamics, mitophagic flux and Nrf2 signalling alleviates sustained mitochondrial dysfunction and oxidative stress and represents a promising therapeutic strategy for IDD; furthermore, our results provide evidence that MitoQ might serve as an effective therapeutic agent for this disorder.

show abstract

“…In recent years, many studies have shown that a variety of factors (such as age [7], high glucose [19,20] [6,12]. In our previous study, we found that H 2 O 2 treatment at a concentration of 200 lM for 6 h induced oxidative stress and cell death.…”

Section: Discussionmentioning

confidence: 98%

“…Briefly, the harvested cells were resuspended in a mixture of 500 lL culture medium and 500 lL JC-1 staining fluid and then incubated for 20 min in the dark at 37°C. After washing with ice-cold staining buffer twice by centrifugation, cells were resuspended in JC-1 staining buffer (19) and analyzed by flow cytometry. The Dwm of each sample was expressed as a ratio of red fluorescence intensity (JC-1 aggregates) over green fluorescence intensity (JC-1 monomers).…”

Section: Measurement Of Mitochondrial Membrane Potential (Dwm)mentioning

confidence: 99%

Pyrroloquinoline quinone protects nucleus pulposus cells from hydrogen peroxide-induced apoptosis by inhibiting the mitochondria-mediated pathway

Yang

Rong

Zeng³

et al. 2014

Eur Spine J

Self Cite

View full text Add to dashboard Cite

show abstract

Reactive oxygen species-mediated mitochondrial dysfunction plays a critical role in high glucose-induced nucleus pulposus cell injury

Cited by 14 publications

References 5 publications

Salidroside attenuates neuroinflammation and improves functional recovery after spinal cord injury through microglia polarization regulation

Salidroside attenuates neuroinflammation and improves functional recovery after spinal cord injury through microglia polarization regulation

The mitochondria‐targeted anti‐oxidant MitoQ protects against intervertebral disc degeneration by ameliorating mitochondrial dysfunction and redox imbalance

Pyrroloquinoline quinone protects nucleus pulposus cells from hydrogen peroxide-induced apoptosis by inhibiting the mitochondria-mediated pathway

Contact Info

Product

Resources

About