Prussian Blue Nanoparticles Stabilize SOD1 from Ubiquitination‐Proteasome Degradation to Rescue Intervertebral Disc Degeneration

Advanced Science, Journal Year: 2022, Volume and Issue: 9(10)

Published: Feb. 6, 2022

Discography often destroys the hypoxic environment in intervertebral disc and accelerates degeneration (IVDD). Therefore, it fails to meet requirements for application clinical practice. This technology mainly increases reactive oxygen species (ROS) IVD. As so, is particularly critical develop strategies avoid this mechanism. Prussian blue nanoparticles (PBNPs) are found enhance development under magnetic resonance T1 have antioxidant enzyme activity. The key results of present study confirm that PBNPs alleviate intracellular oxidative stress increase activities enzymes, such as superoxide dismutase 1 (SOD1). can rescue nucleus pulposus cell by increasing oxidoreductase system-related mRNA proteins, especially stabilizing SOD1 from ubiquitination-proteasome degradation, thus improving mitochondrial structure antioxidation ability, finally rescuing ROS-induced IVDD a rat model. considered be potential antioxidation-protective discography contrast agent.

Language: Английский

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The role of oxidative stress in intervertebral disc degeneration: Mechanisms and therapeutic implications

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 98, P. 102323 - 102323

Published: May 9, 2024

Oxidative stress is one of the main driving mechanisms intervertebral disc degeneration(IDD). has been associated with inflammation in disc, cellular senescence, autophagy, and epigenetics cells. It above pathological are closely linked through common hub reactive oxygen species(ROS), promote each other process degeneration development disease. This reveals important role oxidative IDD, importance great potential IDD therapy targeting stress. The efficacy traditional unstable or cannot be maintained. In recent years, due to rise materials science, many bioactive functional have applied treatment combination drugs, satisfactory achieved. At present, research review antioxidant not complete. Based on existing studies, mechanism were summarized this paper, strategies based emerging reviewed.

Language: Английский

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Sirtuin 3-dependent mitochondrial redox homeostasis protects against AGEs-induced intervertebral disc degeneration

Redox Biology, Journal Year: 2018, Volume and Issue: 19, P. 339 - 353

Published: Sept. 6, 2018

Intervertebral disc (IVD) degeneration contributes largely to pathoanatomical and degenerative changes of spinal structure that increase the risk low back pain. Apoptosis in nucleus pulposus (NP) can aggravate IVD degeneration, increasing studies have shown interventions targeting NP cell apoptosis ameliorate exhibiting their potential for use as therapeutic strategies. Recent data advanced glycation end products (AGEs) accumulate tissues parallel with progression form a microenvironment oxidative stress. This study examined whether AGEs accumulation aggravates explored mechanisms underlying these effects. We observed viability proliferation human cells were significantly suppressed by treatment, mainly due apoptosis. Furthermore, activation mitochondrial pathway was detected after treatment. In addition, molecular showed could generation reactive oxygen species prolonged permeability transition pore, well increased level Bax protein decreased Bcl-2 mitochondria. These effects be reduced antioxidant (2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride (MitoTEMPO) Visomitin (SKQ1). Importantly, we identified impairment Sirtuin3 (SIRT3) function network vital AGEs-induced stress secondary Finally, based on findings nicotinamide mononucleotide (NMN) restore SIRT3 rescue through adenosine monophosphate-activated kinase peroxisome proliferator-activated receptor-γ coactivator 1α (AMPK-PGC-1α) vitro, confirmed its protective effect vivo. conclusion, our demonstrate protects against degeneration. Targeting improve redox homeostasis may represent strategy attenuating AGEs-associated

Language: Английский

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Honokiol alleviates the degeneration of intervertebral disc via suppressing the activation of TXNIP-NLRP3 inflammasome signal pathway

Free Radical Biology and Medicine, Journal Year: 2018, Volume and Issue: 120, P. 368 - 379

Published: April 9, 2018

Language: Английский

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Glycosaminoglycan synthesis in the nucleus pulposus: Dysregulation and the pathogenesis of disc degeneration

Matrix Biology, Journal Year: 2018, Volume and Issue: 71-72, P. 368 - 379

Published: March 1, 2018

Language: Английский

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Restoration of Autophagic Flux Rescues Oxidative Damage and Mitochondrial Dysfunction to Protect against Intervertebral Disc Degeneration

Oxidative Medicine and Cellular Longevity, Journal Year: 2019, Volume and Issue: 2019, P. 1 - 27

Published: Dec. 30, 2019

Oxidative stress-induced mitochondrial dysfunction and nucleus pulposus (NP) cell apoptosis play crucial roles in the development of intervertebral disc degeneration (IDD). Increasing studies have shown that interventions targeting impaired autophagic flux can maintain cellular homeostasis by relieving oxidative damage. Here, we investigated effect curcumin (CUR), a known autophagy activator, on IDD vitro vivo. CUR suppressed tert-butyl hydroperoxide- (TBHP-) induced stress thereby inhibited human NP apoptosis, senescence, ECM degradation. treatment enhanced an AMPK/mTOR/ULK1-dependent manner. Notably, alleviated TBHP-induced interruption autophagosome-lysosome fusion impairment lysosomal function thus contributed to restoration blocked clearance. These protective effects TBHP-stimulated cells resembled produced inducer rapamycin, but were partially eliminated 3-methyladenine- compound C-mediated inhibition initiation or chloroquine-mediated obstruction flux. Lastly, also exerted against puncture-induced progression Our results showed suppression excessive ROS production through enhancement coupled with ameliorated Thus, maintenance proper functioning represents promising therapeutic strategy for IDD, might serve as effective agent IDD.

Language: Английский

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Urolithin A-induced mitophagy suppresses apoptosis and attenuates intervertebral disc degeneration via the AMPK signaling pathway

Free Radical Biology and Medicine, Journal Year: 2020, Volume and Issue: 150, P. 109 - 119

Published: Feb. 24, 2020

Language: Английский

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Mechanosensitive Ion Channel Piezo1 Activated by Matrix Stiffness Regulates Oxidative Stress‐Induced Senescence and Apoptosis in Human Intervertebral Disc Degeneration

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

Mechanical stimulation plays a crucial part in the development of intervertebral disc degeneration (IDD). Extracellular matrix (ECM) stiffness, which is mechanical microenvironment nucleus pulposus (NP) tissue, contributes to pathogenesis IDD. The mechanosensitive ion channel Piezo1 mediates transduction. This study purposed investigate function human NP cells under ECM stiffness. expression and elasticity modulus increased degenerative tissues. Stiff activated intracellular Ca 2+ levels. Moreover, activation reactive oxygen species (ROS) levels GRP78 CHOP, contribute oxidative stress endoplasmic reticulum (ER) stress. Furthermore, stiff aggravated stress‐induced senescence apoptosis cells. inhibition alleviated apoptosis, caused by increase Finally, silencing ameliorated IDD an vivo rat model decreased In conclusion, we identified as transduction mediator for stimulation. Our results provide novel insights into mechanism cells, with potential treating

Language: Английский

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Progerin accumulation in nucleus pulposus cells impairs mitochondrial function and induces intervertebral disc degeneration and therapeutic effects of sulforaphane

Theranostics, Journal Year: 2019, Volume and Issue: 9(8), P. 2252 - 2267

Published: Jan. 1, 2019

Progerin, a truncated unprocessed lamin A protein, causes tissue aging and degeneration. In this study we explored the role of progerin in pathogenesis intervertebral disc degeneration (IDD). We also examined effect sulforaphane (SFN) on accumulation mitochondrial dysfunction IDD. Methods: The IDD was using human nucleus pulposus (NP) tissues, rat NP cells, Lmna G609G knock-in mice. Immunostaining, X-ray imaging, Western blotting were performed to assess phenotypes discs. Alterations senescence apoptosis evaluated by SA-β-galactosidase, immunofluorescence, flow cytometry, TUNEL assays. Mitochondrial function investigated JC-1 staining, transmission electron microscopy, determination level ATP activities enzymes. Results: elevated degenerated tissues. G609G/G609G mice displayed IDD, as evidenced increased matrix metalloproteinase-13 expression decreased collagen II aggrecan height. Furthermore, overexpression cells induced (decreased synthesis, membrane potential, complex enzymes), morphologic abnormalities, disrupted dynamic (abnormal proteins involved fission fusion), resulting senescence. SFN ameliorated progerin-induced defects Conclusions: Progerin is Also, alleviates progerin‑induced which associated with amelioration dysfunction. Thus, shows promise for treatment

Language: Английский

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Parkin and Nrf2 prevent oxidative stress-induced apoptosis in intervertebral endplate chondrocytes via inducing mitophagy and anti-oxidant defenses

Life Sciences, Journal Year: 2019, Volume and Issue: 243, P. 117244 - 117244

Published: Dec. 28, 2019

Language: Английский

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