Lysosomal dysfunction on hydrogen peroxide-induced apoptosis of osteoarthritic chondrocytes

Takahashi, Toshiaki; Kitaoka, Kenichi; Ogawa, Yasuhiro; Kobayashi, Toshihiro; Seguchi, Harumichi; Tani, Tohru; Shoji, Yasuhiro

doi:10.3892/ijmm.14.2.197

Cited by 11 publications

(14 citation statements)

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“…In addition, mitochondrial dysfunction increases ROS production. 54,55 When the cellular production of ROS overwhelms the intrinsic antioxidant capacity, it causes oxidative stress and results in damage to DNAs, proteins, and lipids. 54,56,57 This process is thought to contribute to the pathogenesis of a number of neurodegenerative disorders.…”

Section: Discussionmentioning

confidence: 99%

Neuroglobin Is an Endogenous Neuroprotectant for Retinal Ganglion Cells against Glaucomatous Damage

Wei

Cho

et al. 2011

The American Journal of Pathology

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Neuroglobin (NGB), a newly discovered member of the globin superfamily, may regulate neuronal survival under hypoxia or oxidative stress. Although NGB is greatly expressed in retinal neurons, the biological functions of NGB in retinal diseases remain largely unknown. We investigated the role of NGB in an experimental model of glaucoma, a neurodegenerative disorder that usually involves elevation of intraocular pressure (IOP). Elevated IOP is thought to induce oxidative stress in retinal ganglion cells (RGCs), thereby causing RGC death and, eventually, blindness. We found that NGB plays a critical role in increasing RGC resistance to ocular hypertension and glaucomatous damage. Neuroglobin (NGB) is a novel member of the globin superfamily that is distantly related to hemoglobin and myoglobin. 1 A highly conserved protein in evolution, human and mouse Ngb, both comprised of 151 amino acids, are 94% identical. 2,3 In mammals, expression of NGB is found in the brain, retina, and other nerve tissues, predominantly in neurons but absent from glial cells. 4 -7 Distribution of NGB protein in the normal human retina is very similar to what has been described in mice: NGB is detected primarily in the plexiform layers and photoreceptor inner segments, which are rich in mitochondria and synapses and consume high amounts of oxygen. 8,9 NGB has been shown to act as an endogenous neuroprotective molecule that enhances neuronal survival under hypoxic-ischemic insults in the brain 10 -12 ; however, its physiological functions and molecular mode of actions are not fully understood. Of note, NGB is present at a 100-fold greater concentration in the retina than in the brain, 8,[13][14][15] suggesting that the retina may be its most important site of function; however, among the many unknown roles of NGB, functional significance of NGB expression in the retina has been largely unexplored.

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Section: Discussionmentioning

confidence: 99%

Neuroglobin Is an Endogenous Neuroprotectant for Retinal Ganglion Cells against Glaucomatous Damage

Wei

Cho

et al. 2011

The American Journal of Pathology

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“…The mechanism of apoptosis induction by oxidative stress had been attributed to LMP in several studies, by releasing lysosomal enzymes into the cytosol, activating caspases and other toxic cascades [38,45,54]. Takahashi et al [46] reported that lysosomal dysfunction with swelling and rupture was closely associated with the ROS formation that occurred after the addition of H 2 O 2 to osteoarthritic chondrocytes at the early period of apoptosis. Thus, we suggested that maintaining the integrity of lysosome and normal function of mitochondria might be crucial for the survival of NP cells.…”

Section: Discussionmentioning

confidence: 99%

“…It was recognized as an important cellular stress with significant pathological implications in many disease processes [45]. There were reports that H 2 O 2 induced cartilage destruction in vivo through increasing apoptosis of chondrocytes, and resulted in osteoarthritis ultimately [46,47]. There were also reports that H 2 O 2 led to dysfunction and increased apoptosis of osteoblasts, thus contributed to the development of osteonecrosis [41,48].…”

Section: Discussionmentioning

confidence: 99%

The Responses of Autophagy and Apoptosis to Oxidative Stress in Nucleus Pulposus Cells: Implications for Disc Degeneration

Chen

et al. 2014

Cell Physiol Biochem

155

126

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Background/Aims: Apoptosis and autophagy are two patterns of programmed cell death which play important roles in the intervertebral disc degeneration. Oxidative stress is an important factor for the induction of programmed cell death. However, the cellular reactions linking autophagy to apoptosis of disc cells under oxidative stress have never been described. This study investigated the responses of autophagy and apoptosis and their interactions in the nucleus pulposus cells (NP cells) under oxidative stress, with the aim to better understand the mechanism of disc degeneration. Methods: NP cells isolated from rat lumbar discs were subjected to different concentrations of H₂O₂ for various time periods. Cell viability was determined by CCK-8 assay, and their apoptosis and autophagy responses were evaluated by fluorescent analysis, flow cytometry and western blotting, et al. The interactions of autophagy and apoptosis and the possible signaling pathways were also investigated by using autophagy modulators. Results: H₂O₂ increased the lysosomal membrane permeability in the NP cells and induced apoptosis through the mitochondrial pathway subsequently. Meanwhile, H₂O₂ stimulated an early autophagy response through the ERK/m-TOR signaling pathway. Autophagy inhibition significantly decreased the apoptosis incidence in the cells insulted by H₂O₂. Conclusion: These results suggested that controlling the autophagy response in the NP cells under oxidative stress should be beneficial for the survival of the cells and probably delay the process of disc degeneration.

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“…49 Lysosomal swelling was detected after one hour of application of 0.1 mM H 2 O 2 and over, possibly revealing lysosomal membrane instability. Moreover, indications of lysosomal rupture, including release of lysosomal enzymes, were apparent one hour after the addition of 10 mM of H 2 O 2 .…”

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confidence: 99%

“…The addition of H 2 O 2 to chondrocytes may induce ROS formation and lysosomal dysfunction, revealed by swelling and rupture, prior to dysfunction of the mitochondrial membrane potential. 49 Jiang et al 50 demonstrated that glucosamine protects nucleus pulposus cells (NPC) and induces autophagy via the mammalian target of rapamycin-dependent pathway. They also showed that glucosamine attenuated the decrease of aggrecan and prevented the apoptosis of the NPC induced by IL-1b.…”

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confidence: 99%

Hydrogen Peroxide-Induced Oxidative Damage in Human Chondrocytes: The Prophylactic Effects of Hypericum Perforatum Linn Extract on Deoxyribonucleic acid Damage, Apoptosis and Matrix Remodeling by a Disintegrin-Like and Metalloproteinase With Thrombospondin Motifs Proteinases

et al. 2014

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Objectives: This in vitro study aimed to examine the protective roles of Hypericum perforatum Linn (HPL) extract on cell viability, DNA damage, apoptosis and a disintegrin-like and metalloproteinase with thrombospondin motifs (ADAMTS) proteins in chondrocytes induced by hydrogen peroxide (H2O2), as a model of chondrocytes subjected to reactive oxygen species (ROS) attack in rheumatoid arthritis and osteoarthritis. Materials and methods: Human chondrosarcoma cell line (OUMS-27) was used. Cells were incubated with different concentrations of methanolic extract (100, 400, and 750 μg/ml) of HPL for 36 hours, and then treated with 0.7 mM H2O2 for two hours. Trypan blue was used for evaluation of cell viability, while DNA damage was evaluated by alkaline Comet assay. Caspase-1, ADAMTS5, ADAMTS9, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) proteins were analyzed by Western blot. Results: In vitro H2O2 treatment decreased OUMS-27 cell viability. Cells pretreated with HPL at concentration of 400 μg/mL were best protected from H2O2 toxicity. Compared to 100 μg/ml concentration, pretreatment of cells with 750 or 400 μg/ml of HPL generated more protection against H2O2-induced DNA damage. Hydrogen peroxide application to the cells led to a slight increase in Caspase-1 expression, which shows no apoptosis. The most prominent increase in Caspase-1 level was shown in cells treated with 400 μg/ml of HPL extract. There was an increase in ADAMTS9 and a decrease in ADAMTS5 levels upon H2O2 administration. Pretreatment with HPL led to more decrease in ADAMTS5 level, indicating the protection of extracellular matrix attacked by these proteinases in cartilage tissue. Conclusion: It can be concluded that HPL has a potential to reverse the negative effects and processes induced by H2O2 in OUMS-27 cells and it can protect the surrounding cartilage area of chondrocytes from oxidative damage, which is suggested to be one of the main molecular factors accused for progression of rheumatoid arthritis and osteoarthritis.

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Lysosomal dysfunction on hydrogen peroxide-induced apoptosis of osteoarthritic chondrocytes

Cited by 11 publications

References 0 publications

Neuroglobin Is an Endogenous Neuroprotectant for Retinal Ganglion Cells against Glaucomatous Damage

Neuroglobin Is an Endogenous Neuroprotectant for Retinal Ganglion Cells against Glaucomatous Damage

The Responses of Autophagy and Apoptosis to Oxidative Stress in Nucleus Pulposus Cells: Implications for Disc Degeneration

Hydrogen Peroxide-Induced Oxidative Damage in Human Chondrocytes: The Prophylactic Effects of Hypericum Perforatum Linn Extract on Deoxyribonucleic acid Damage, Apoptosis and Matrix Remodeling by a Disintegrin-Like and Metalloproteinase With Thrombospondin Motifs Proteinases

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