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

Yang, Lianjun; Rong, Zijie; Zeng, Mingjun; Cao, Yanlin; Gong, Xumeng; Li, Lin; Chen, Yong; Cao, Wei; Zhu, Lixin; Wang, Dong

doi:10.1007/s00586-014-3630-2

Cited by 58 publications

(47 citation statements)

References 29 publications

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“…Apoptosis decreases the number of functional and viable disc cells, which is one of the triggers of IDD [80, 81]. ROS have been determined as a potent proapoptotic factor for human, rat, and rabbit NP cells in vitro [38, 40, 41, 44]. H 2 O 2 increased lysosome membrane permeability and decreased MTMP in rat NP cells.…”

Section: The Roles Of Oxidative Stress In the Pathogenesis Of Iddmentioning

confidence: 99%

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ROS: Crucial Intermediators in the Pathogenesis of Intervertebral Disc Degeneration

Feng

Yang

Lan

et al. 2017

Oxidative Medicine and Cellular Longevity

297

262

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Excessive reactive oxygen species (ROS) generation in degenerative intervertebral disc (IVD) indicates the contribution of oxidative stress to IVD degeneration (IDD), giving a novel insight into the pathogenesis of IDD. ROS are crucial intermediators in the signaling network of disc cells. They regulate the matrix metabolism, proinflammatory phenotype, apoptosis, autophagy, and senescence of disc cells. Oxidative stress not only reinforces matrix degradation and inflammation, but also promotes the decrease in the number of viable and functional cells in the microenvironment of IVDs. Moreover, ROS modify matrix proteins in IVDs to cause oxidative damage of disc extracellular matrix, impairing the mechanical function of IVDs. Consequently, the progression of IDD is accelerated. Therefore, a therapeutic strategy targeting oxidative stress would provide a novel perspective for IDD treatment. Various antioxidants have been proposed as effective drugs for IDD treatment. Antioxidant supplementation suppresses ROS production in disc cells to promote the matrix synthesis of disc cells and to prevent disc cells from death and senescence in vitro. However, there is not enough in vivo evidence to support the efficiency of antioxidant supplementation to retard the process of IDD. Further investigations based on in vivo and clinical studies will be required to develop effective antioxidative therapies for IDD.

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Section: The Roles Of Oxidative Stress In the Pathogenesis Of Iddmentioning

confidence: 99%

“…H 2 O 2 increased lysosome membrane permeability and decreased MTMP in rat NP cells. As a result, ROS were overproduced to induce NP cell apoptosis through the mitochondrial apoptosis pathway [22, 41]. Notochordal cell apoptosis is recognized as the starting point of IDD.…”

Section: The Roles Of Oxidative Stress In the Pathogenesis Of Iddmentioning

confidence: 99%

ROS: Crucial Intermediators in the Pathogenesis of Intervertebral Disc Degeneration

Feng

Yang

Lan

et al. 2017

Oxidative Medicine and Cellular Longevity

297

262

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“…In the present study, hydrogen peroxide (H 2 O 2 ) was used as a stimulus to study the effect of oxidative stress on nucleus pulposus cell injury and underlying mechanisms (8). The study determined that the protective effect of aloperine attenuates H 2 O 2 -induced injury via its activation of AKT and suppression of the nuclear factor-κB (NF-κB) pathway.…”

Section: Introductionmentioning

confidence: 99%

“…When these defense mechanisms cannot prevent the generation of excessive reactive oxygen species, oxidative stress will occur, which causes the degeneration of cells or protein tissue, lipid oxidation, DNA damage and other physiological dysfunctional processes, leading to apoptosis (7). However, only a limited number of studies have focused on intervertebral disc degeneration and the apoptosis of nucleus pulposus cells due to oxidative stress (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Aloperine attenuates hydrogen peroxide-induced injury via anti-apoptotic activity and suppression of the nuclear factor-κB signaling pathway

Ren

Guo

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Aloperine is an alkaloid that exerts significant inhibitive effects on acute inflammation and Type Ⅲ and Ⅳ hypersensitivity caused by a variety of inflammatory agents. The aims of the present study were to investigate whether the protective effect of aloperine attenuates hydrogen peroxide (H 2 O 2 )-induced injury, and to identify the underlying mechanisms involved. Nucleus pulposus cells were extracted from adult male Sprague-Dawley rats, and incubated with fresh medium containing 200 µM H 2 O 2 for 24 h. In the study, treatment with aloperine significantly increased cell viability and suppressed apoptosis in H 2 O 2 -treated nucleus pulposus cells in a dose-dependent manner. In addition, 10 and 100 nM aloperine significantly inhibited H 2 O 2 -induced tumor necrosis factor-α and interleukin-6 activities, and significantly increased the H 2 O 2 -reduced superoxide dismutase and glutathione peroxidase activities in nucleus pulposus cells (all P<0.01). However, aloperine treatment (10 and 100 nM) significantly reduced the H 2 O 2 -induced caspase-9 activity in nucleus pulposus cells. Furthermore, addition of 10 and 100 nM aloperine significantly suppressed nuclear factor-κB (NF-κB) and phosphorylated-protein kinase B expression levels in H 2 O 2 -treated nucleus pulposus cells. In conclusion, the protective effect of aloperine attenuated H 2 O 2 -induced injury via hyperproliferation, its anti-apoptotic activity and suppression of the NF-κB signaling pathway.

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“…ROS have been regarded as potential pro-apoptotic factors for NP cells in vitro [38,40,41,44]. ROS accumulation has been shown to induce NP cell apoptosis through the mitochondrial apoptosis pathway and the death receptor pathway [12][13][14]. Additionally, many external stimuli can cause intracellular ROS accumulation, such as mechanical overloading, nutrition deprivation, and inflammatory cytokines [15,16].…”

Section: Introductionmentioning

confidence: 99%

Aquaporin-3 Attenuates Oxidative Stress-Induced Nucleus Pulposus Cell Apoptosis Through Regulating the P38 MAPK Pathway

Yao

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Previous studies have shown that oxidative damage is a main contributor to disc nucleus pulposus (NP) cell apoptosis. Aquaporin-3 (AQP-3) facilitates reactive oxygen species (ROS) scavenging and thus alleviates oxidative injury in other cells. This study aims to investigate the role and mechanism of AQP-3 in regulating NP cell apoptosis under oxidative damage. Methods: Rat NP cells were treated with H₂O₂ for 48 hours, while control NP cells were free of H₂O₂. Recombinant AQP-3 lentiviral vectors were used to investigate the effect of enhanced AQP-3 expression levels in NP cells. NP cell apoptosis was assessed by flow cytometry, caspase-3 activity, gene expression of apoptosis-related molecules (Bax, Bcl-2 and caspase-3), and protein expression of cellular apoptosis markers (cleaved PARP and cleaved caspase-3). Additionally, intracellular ROS content and activity of the p38 MAPK pathway were evaluated. Results: Compared with the control NP cells, oxidative damage in the treatment cells significantly increased cell apoptosis ratios and caspase-3 activity, upregulated gene expression of Bax and caspase-3, downregulated gene expression of Bcl-2, and increased protein expression of cleaved PARP and cleaved caspase-3, as well as increased intracellular ROS content and activity of the p38 MAPK pathway. However, AQP-3 overexpression partly alleviated cell apoptosis, decreased intracellular ROS content, and inhibited the p38 MAPK pathway in NP cells under oxidative damage. Conclusion: Oxidative damage can significantly downregulate AQP-3 expression. Enhancing AQP-3 expression in NP cells partly attenuates cellular apoptosis through regulating the p38 MAPK pathway under oxidative damage.

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

Abstract: Our results suggest that PQQ can protect rat NP cells against oxidative stress via a mitochondria-mediated pathway. PQQ might be useful as a potential pharmaceutical agent in the prevention of intervertebral disc degeneration.

Cited by 58 publications

References 29 publications

ROS: Crucial Intermediators in the Pathogenesis of Intervertebral Disc Degeneration

ROS: Crucial Intermediators in the Pathogenesis of Intervertebral Disc Degeneration

Aloperine attenuates hydrogen peroxide-induced injury via anti-apoptotic activity and suppression of the nuclear factor-κB signaling pathway

Aquaporin-3 Attenuates Oxidative Stress-Induced Nucleus Pulposus Cell Apoptosis Through Regulating the P38 MAPK Pathway

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