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

Kang, Liang; Liu, Shiwei; Li, Jingchao; Tian, Yueyang; Xue, Yuan; Liu, Xiaozhi

doi:10.1016/j.lfs.2019.117244

Cited by 82 publications

(63 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In human NP cells, cellular senescence could be also due to excessive ROS accumulation and subsequent oxidative stress. Moreover, oxidative stress-induced apoptosis and senescence contribute to IDD progression [ 14 ]. The present results indicated that stiff ECM increases intracellular ROS, activates oxidative stress, and aggravates oxidative stress-induced apoptosis and senescence.…”

Section: Discussionmentioning

confidence: 99%

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

Wang

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Mechanical stimulation plays a crucial part in the development of intervertebral disc degeneration (IDD). Extracellular matrix (ECM) stiffness, which is a crucial mechanical microenvironment of the nucleus pulposus (NP) tissue, contributes to the pathogenesis of IDD. The mechanosensitive ion channel Piezo1 mediates mechanical transduction. This study purposed to investigate the function of Piezo1 in human NP cells under ECM stiffness. The expression of Piezo1 and the ECM elasticity modulus increased in degenerative NP tissues. Stiff ECM activated the Piezo1 channel and increased intracellular Ca2+ levels. Moreover, the activation of Piezo1 increased intracellular reactive oxygen species (ROS) levels and the expression of GRP78 and CHOP, which contribute to oxidative stress and endoplasmic reticulum (ER) stress. Furthermore, stiff ECM aggravated oxidative stress-induced senescence and apoptosis in human NP cells. Piezo1 inhibition alleviated oxidative stress-induced senescence and apoptosis, caused by the increase in ECM stiffness. Finally, Piezo1 silencing ameliorated IDD in an in vivo rat model and decreased the elasticity modulus of rat NP tissues. In conclusion, we identified the mechanosensitive ion channel Piezo1 in human NP cells as a mechanical transduction mediator for stiff ECM stimulation. Our results provide novel insights into the mechanism of mechanical transduction in NP cells, with potential for treating IDD.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Wang

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…The majority of the findings showing a direct regulation of these two processes support the idea that mitophagy occurs as a pro-survival mechanism. Prevention of mitophagy, by Parkin and/or PINK1 inhibition, or by cyclosporine A or 3-MA treatment, induced CytC release and caspase activity, stimulating apoptosis ( Tian et al, 2019 ; Kang et al, 2020 ; Li C. et al, 2020 ; Lin et al, 2020 ). Consistently, mitophagy induction via Urolithin A or FCCP treatment prevented apoptosis ( Tian et al, 2019 ; Lin et al, 2020 ).…”

Section: Mitophagy: a Pro-survival Or A Pro-apoptotic Mechanism?mentioning

confidence: 99%

Role of Mitofusins and Mitophagy in Life or Death Decisions

Joaquim

Escobar-Henriques

2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Mitochondria entail an incredible dynamism in their morphology, impacting death signaling and selective elimination of the damaged organelles. In turn, by recycling the superfluous or malfunctioning mitochondria, mostly prevalent during aging, mitophagy contributes to maintain a healthy mitochondrial network. Mitofusins locate at the outer mitochondrial membrane and control the plastic behavior of mitochondria, by mediating fusion events. Besides deciding on mitochondrial interconnectivity, mitofusin 2 regulates physical contacts between mitochondria and the endoplasmic reticulum, but also serves as a decisive docking platform for mitophagy and apoptosis effectors. Thus, mitofusins integrate multiple bidirectional inputs from and into mitochondria and ensure proper energetic and metabolic cellular performance. Here, we review the role of mitofusins and mitophagy at the crossroad between life and apoptotic death decisions. Furthermore, we highlight the impact of this interplay on disease, focusing on how mitofusin 2 and mitophagy affect non-alcoholic fatty liver disease.

show abstract

“…Recently, Williams et al observed a hypermethylation level at one cytosine guanine (CpG) site (cg15832436) of the parkinson protein 2 (PARK2) promoter in IDD [ 95 ]. The modification of PARK2 at transcriptional level may regulate mitochondrial-associated OS in degenerative NP and EP cells via parkin-mediated mitophagy [ 96 , 97 ]. Therefore, epigenetic changes may affect cellular senescence via the regulation of OS at transcriptional level.…”

Section: The Underlying Pathogenesis Of Cell Senescence In Iddmentioning

confidence: 99%

Cell Senescence: A Nonnegligible Cell State under Survival Stress in Pathology of Intervertebral Disc Degeneration

Zhang

Yang

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

The intervertebral disc degeneration (IDD) with increasing aging mainly manifests as low back pain (LBP) accompanied with a loss of physical ability. These pathological processes can be preliminarily interpreted as a series of changes at cellular level. In addition to cell death, disc cells enter into the stagnation with dysfunction and deteriorate tissue microenvironment in degenerative discs, which is recognized as cell senescence. During aging, many intrinsic and extrinsic factors have been proved to have strong connections with these cellular senescence phenomena. Growing evidences of these connections require us to gather up critical cues from potential risk factors to pathogenesis and relative interventions for retarding cell senescence and attenuating degenerative changes. In this paper, we try to clarify another important cell state apart from cell death in IDD and discuss senescence-associated changes in cells and extracellular microenvironment. Then, we emphasize the role of oxidative stress and epigenomic perturbations in linking risk factors to cell senescence in the onset of IDD. Further, we summarize the current interventions targeting senescent cells that may exert the benefits of antidegeneration in IDD.

show abstract

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

Cited by 82 publications

References 50 publications

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

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

Role of Mitofusins and Mitophagy in Life or Death Decisions

Cell Senescence: A Nonnegligible Cell State under Survival Stress in Pathology of Intervertebral Disc Degeneration

Contact Info

Product

Resources

About