Exercise-induced FNDC5/irisin protects nucleus pulposus cells against senescence and apoptosis by activating autophagy

Zhou, Wenxian; Shi, Yifeng; Wang, Hui; Chen, Linjie; Yu, Caiyu; Zhang, Xufei; Yang, Lei; Zhang, Xiaolei; Wu, Ai-Min

doi:10.1038/s12276-022-00811-2

Cited by 32 publications

(23 citation statements)

References 53 publications

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“…IVDD is a chronic process that commonly causes LBP; however, the specific cause of IVDD remains unclear. Published studies have demonstrated that IVDD is a complex process with multifactorial interactions, which is primarily characterized by ECM destruction and cell phenotype changes, as well as apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis of IVD ( 31 , 104 – 107 ). The term ferroptosis was first coined in 2012.…”

Section: Ferroptosis and Ivddmentioning

confidence: 99%

Ferroptosis: A potential target for the intervention of intervertebral disc degeneration

et al. 2022

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Ferroptosis, an iron-dependent form of programmed cell death marked by phospholipid peroxidation, is regulated by complex cellular metabolic pathways including lipid metabolism, iron balance, redox homeostasis, and mitochondrial activity. Initial research regarding the mechanism of ferroptosis mainly focused on the solute carrier family 7 member 11/glutathione/glutathione peroxidase 4 (GPX4) signal pathway. Recently, novel mechanisms of ferroptosis, independent of GPX4, have been discovered. Numerous pathologies associated with extensive lipid peroxidation, such as drug-resistant cancers, ischemic organ injuries, and neurodegenerative diseases, are driven by ferroptosis. Ferroptosis is a new therapeutic target for the intervention of IVDD. The role of ferroptosis in the modulation of intervertebral disc degeneration (IVDD) is a significant topic of interest. This is a novel research topic, and research on the mechanisms of IVDD and ferroptosis is ongoing. Herein, we aim to review and discuss the literature to explore the mechanisms of ferroptosis, the relationship between IVDD and ferroptosis, and the regulatory networks in the cells of the nucleus pulposus, annulus fibrosus, and cartilage endplate to provide references for future basic research and clinical translation for IVDD treatment.

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Section: Ferroptosis and Ivddmentioning

confidence: 99%

Ferroptosis: A potential target for the intervention of intervertebral disc degeneration

et al. 2022

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“…31 Irisin could also protect nucleus pulposus cells against senescence and apoptosis by activating autophagy. 32 And our previous study has also shown that irisin can activate the Akt/eNOS pathway which considered as a survival pathway, and Akt/eNOS pathway may play an important role in the anti-apoptosis effects of irisin.…”

Section: Discussionmentioning

confidence: 91%

“…Previous studies have shown that irisin could inhibit apoptosis including cardiomyocyte apoptosis, endothelial cell apoptosis and pancreatic β cell apoptosis by the Akt, ERK, p38 MAPK, and TLR/MyD88 signaling pathway 31 . Irisin could also protect nucleus pulposus cells against senescence and apoptosis by activating autophagy 32 . And our previous study has also shown that irisin can activate the Akt/eNOS pathway which considered as a survival pathway, and Akt/eNOS pathway may play an important role in the anti‐apoptosis effects of irisin.…”

Section: Discussionmentioning

confidence: 98%

Irisin inhibits NLRP3 inflammasome activation in HG/HF incubated cardiac microvascular endothelial cells with H/R injury

Xin¹,

Zhang

Hao³

et al. 2022

Microcirculation

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Purpose: NLRP3 inflammasome mediates myocardial ischemia/reperfusion (MI/R) injury and diabetic vascular endothelia dysfunction. However, the role of NLRP3 inflammasome in MI/R injury with diabetes has not been fully described. Irisin plays an important role in anti-inflammation and improves endothelial function in type 2 diabetes. The current study aimed to investigate the effect of irisin on regulating NLRP3 inflammasome activation in diabetic vascular endothelia dysfunction. Methods: Cardiac microvascular endothelial cells (CMECs) were cultured and subjected to high glucose/high fat (HG/HF) receiving hypoxia/reoxygenation (H/R) with irisin incubation or not. Then, apoptosis, viability, migration, NO secretion, and inflammasome activation were examined. Results: The hypoxic CMECs exhibited increased apoptosis, impaired viability, and migration, even decreased NO secretion and enhanced inflammasome activation. Moreover, irisin incubation decreased NLRP3 activation and attenuated cell injury in HG/HF cultured CMECs subjected to H/R injury, which was abolished by NLRP3 inflammasome activation. Meanwhile, NLRP3 inflammasome siRNA also attenuated H/R injury in CMECs under HG/HF condition. Conclusion:The current study demonstrated for the first time that irisin inhibits NLRP3 inflammasome activation in CMECs as a novel mechanism in myocardial ischemia/reperfusion injury in diabetes.

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“…Degenerative discs show reduced brightness and volume. After 8 weeks, the intervertebral discs were scored by the Pfirrmann grading according to the previous research methods [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

“…After decalcification, dehydration and paraffin embedding were carried out, and then dewaxing, hematoxylin and eosin (H&E) staining, and Safranin-O/fast green staining were carried out. Histological scoring methods refer to previous studies [ 25 ]. ERS-related proteins (caspase-3, GRP78, and CHOP) were detected by immunohistochemistry.…”

Section: Methodsmentioning

confidence: 99%

Sulforaphane Delays Intervertebral Disc Degeneration by Alleviating Endoplasmic Reticulum Stress in Nucleus Pulposus Cells via Activating Nrf-2/HO-1

Lin

et al. 2023

Oxidative Medicine and Cellular Longevity

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Intervertebral disc degeneration (IVDD) is one of the main causes of low back pain, which brings heavy burdens to individuals and society. The mechanism of IVDD is complex and diverse. One of the important reasons is that the abnormal accumulation of reactive oxygen species (ROS) in nucleus pulposus cells (NPCs) leads to endoplasmic reticulum stress (ERS), which causes increased apoptosis of NPCs. Nuclear factor E2-related factor 2 (Nrf-2) and its downstream antioxidant proteins are key molecular switches for sensing oxidative stress and regulating antioxidant responses in cells. Sulforaphane (SFN), a natural compound derived from Brassicaceae plants, is a Nrf-2 agonist that displays potent antioxidant potential in vitro and in vivo. Here, we used advanced glycation end products (AGEs) to construct an in vitro degeneration model of NPCs, and we found that AGEs elevated ROS level in NPCs and caused severe ERS and apoptosis. While SFN can promote the entry of Nrf-2 into the nucleus and increase the expression level of heme oxygenase 1 (HO-1) in vitro, thus clearing the accumulated ROS in cells and alleviating ERS and cell apoptosis. Moreover, the protection of SFN on NPCs was greatly attenuated after HO-1 was inhibited. We also used AGEs to construct a rat IVDD model. Consistent with the in vitro experiments, SFN could attenuate ERS in NPCs in vivo and delay disc degeneration in rats. This study found that SFN can be used as a new and promising agent for the treatment of IVDD.

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Exercise-induced FNDC5/irisin protects nucleus pulposus cells against senescence and apoptosis by activating autophagy

Cited by 32 publications

References 53 publications

Ferroptosis: A potential target for the intervention of intervertebral disc degeneration

Ferroptosis: A potential target for the intervention of intervertebral disc degeneration

Irisin inhibits NLRP3 inflammasome activation in HG/HF incubated cardiac microvascular endothelial cells with H/R injury

Sulforaphane Delays Intervertebral Disc Degeneration by Alleviating Endoplasmic Reticulum Stress in Nucleus Pulposus Cells via Activating Nrf-2/HO-1

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