Orientin downregulating oxidative stress-mediated endoplasmic reticulum stress and mitochondrial dysfunction through AMPK/SIRT1 pathway in rat nucleus pulposus cells in vitro and attenuated intervertebral disc degeneration in vivo

Zhang, Zhao; Wu, Jingtao; Chen, Teng; Wang, Jinquan; Yu, Jiapei; Jin, Chen; Wang, Libo; Wu, Long; Lin, Zhen; Zhou, Yu; Lin, Zhong-Ke

doi:10.1007/s10495-022-01770-9

Cited by 27 publications

(18 citation statements)

References 47 publications

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“…Mechanistic studies revealed that CUR induced autophagy to attenuate oxidative damage and delay IDD in NPCs in an AMPK/mTOR/ULK1 dependent manner 130 . Recently, Zhang et al 131 found that orientin (Ori) ameliorates TBHP‐induced oxidative stress, apoptosis, mitochondrial dysfunction and endoplasmic reticulum (ER) stress in NPCs by activating the SIRT1/AMPK signalling axis. These pieces of evidence suggest that AMPK signalling pathway plays an important role in IDD, and the activation of this pathway is expected to delay IDD.…”

Section: Oxidative Stress and Intracellular Signal Transductionmentioning

confidence: 99%

Oxidative stress in intervertebral disc degeneration: Molecular mechanisms, pathogenesis and treatment

et al. 2023

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Low back pain (LBP) is a leading cause of labour loss and disability worldwide, and it also imposes a severe economic burden on patients and society. Among symptomatic LBP, approximately 40% is caused by intervertebral disc degeneration (IDD). IDD is the pathological basis of many spinal degenerative diseases such as disc herniation and spinal stenosis. Currently, the therapeutic approaches for IDD mainly include conservative treatment and surgical treatment, neither of which can solve the problem from the root by terminating the degenerative process of the intervertebral disc (IVD). Therefore, further exploring the pathogenic mechanisms of IDD and adopting targeted therapeutic strategies is one of the current research hotspots. Among the complex pathophysiological processes and pathogenic mechanisms of IDD, oxidative stress is considered as the main pathogenic factor. The delicate balance between reactive oxygen species (ROS) and antioxidants is essential for maintaining the normal function and survival of IVD cells. Excessive ROS levels can cause damage to macromolecules such as nucleic acids, lipids, and proteins of cells, affect normal cellular activities and functions, and ultimately lead to cell senescence or death. This review discusses the potential role of oxidative stress in IDD to further understand the pathophysiological processes and pathogenic mechanisms of IDD and provides potential therapeutic strategies for the treatment of IDD.

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Section: Oxidative Stress and Intracellular Signal Transductionmentioning

confidence: 99%

Oxidative stress in intervertebral disc degeneration: Molecular mechanisms, pathogenesis and treatment

et al. 2023

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“…Stressors such as inflammation, hypoxia and oxidative stress can promote AMPK phosphorylation and compensate for its anti-inflammatory and anti-ER stress effects. [52][53][54] Our data suggest that irisin increases the level of phosphorylated AMPK. Whether irisin activates AMPK directly or through some intermediate receptor has not been determined.…”

Section: Appropriate Level Of Er Stress Can Regulate the Metabolism Andmentioning

confidence: 56%

Irisin attenuates ventilator‐induced diaphragmatic dysfunction by inhibiting endoplasmic reticulum stress through activation of AMPK

Zhang,

Tu,

Guan

et al. 2024

J Cellular Molecular Medi

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Mechanical ventilation (MV) is an essential life‐saving technique, but prolonged MV can cause significant diaphragmatic dysfunction due to atrophy and decreased contractility of the diaphragm fibres, called ventilator‐induced diaphragmatic dysfunction (VIDD). It is not clear about the mechanism of occurrence and prevention measures of VIDD. Irisin is a newly discovered muscle factor that regulates energy metabolism. Studies have shown that irisin can exhibit protective effects by downregulating endoplasmic reticulum (ER) stress in a variety of diseases; whether irisin plays a protective role in VIDD has not been reported. Sprague–Dawley rats were mechanically ventilated to construct a VIDD model, and intervention was performed by intravenous administration of irisin. Diaphragm contractility, degree of atrophy, cross‐sectional areas (CSAs), ER stress markers, AMPK protein expression, oxidative stress indicators and apoptotic cell levels were measured at the end of the experiment.Our findings showed that as the duration of ventilation increased, the more severe the VIDD was, the degree of ER stress increased, and the expression of irisin decreased.ER stress may be one of the causes of VIDD. Intervention with irisin ameliorated VIDD by reducing the degree of ER stress, attenuating oxidative stress, and decreasing the apoptotic index. MV decreases the expression of phosphorylated AMPK in the diaphragm, whereas the use of irisin increases the expression of phosphorylated AMPK. Irisin may exert its protective effect by activating the phosphorylated AMPK pathway.

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“…Animal experiments have further proven that the expression of ER stress-related markers is related to the degeneration grade and senescence of rat intervertebral discs (Xie et al, 2017). Previous studies showed that the degree of apoptosis in intervertebral discs was lower than that of the control group after CHOP gene knockout, and MRI signal and histological scores were significantly improved after injection of CHOP shRNA into rats (Zhang et al, 2011). Overall, prolonged activation of IRE1α and CHOP can trigger apoptosis under physiological and pathophysiological conditions (Szegezdi et al, 2006).…”

Section: Discussionmentioning

confidence: 94%

“…Thapsigargin (Tg), a classical inducer of ER stress in vitro, can increase cytoplasmic Ca 2+ levels by suppressing cells from pumping Ca 2+ back into the ER (Sikkeland et al, 2019;Zhang et al, 2014). In addition, Tg has been widely acknowledged as a commonly used activator of ER stress and ER stress-related changes in NP cells in ex vivo studies on IVDD (Krupkova et al, 2018;Novais et al, 2021;Yang et al, 2022;Zhang et al, 2022b).…”

Section: Introductionmentioning

confidence: 99%

Sal003 alleviated intervertebral disc degeneration by inhibiting apoptosis and extracellular matrix degradation through suppressing endoplasmic reticulum stress pathway in rats

Chen

et al. 2023

Front. Pharmacol.

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Apoptosis and extracellular matrix degradation of the nucleus pulposus are the main initiators of intervertebral disc degeneration (IVDD) and can be explained by endoplasmic reticulum (ER) stress. Thus, pharmacological therapy aimed at suppressing this pathway may be a promising approach for the management of intervertebral disc degeneration. In this study, we aimed to explore the protective effects of Sal003 against intervertebral disc degeneration and its underlying mechanisms. Thapsigargin (Tg)-stimulated rat nucleus pulposus cells and a needle puncture-induced intervertebral disc degeneration rat model were used to explore the protective effects of Sal003. Our results showed that Sal003 inhibited apoptosis and extracellular matrix degradation by suppressing the endoplasmic reticulum stress pathway. The therapeutic effects of Sal003 were also observed in the intervertebral disc degeneration rat model, as evidenced by improved degeneration along with decreased apoptosis and extracellular matrix degradation in intervertebral discs. Our results demonstrated Sal003 as a potential treatment for intervertebral disc degeneration.

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Orientin downregulating oxidative stress-mediated endoplasmic reticulum stress and mitochondrial dysfunction through AMPK/SIRT1 pathway in rat nucleus pulposus cells in vitro and attenuated intervertebral disc degeneration in vivo

Cited by 27 publications

References 47 publications

Oxidative stress in intervertebral disc degeneration: Molecular mechanisms, pathogenesis and treatment

Oxidative stress in intervertebral disc degeneration: Molecular mechanisms, pathogenesis and treatment

Irisin attenuates ventilator‐induced diaphragmatic dysfunction by inhibiting endoplasmic reticulum stress through activation of AMPK

Sal003 alleviated intervertebral disc degeneration by inhibiting apoptosis and extracellular matrix degradation through suppressing endoplasmic reticulum stress pathway in rats

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