Nucleus pulposus cell apoptosis is attenuated by CDMP-2 through regulating oxidative damage under the hyperosmotic environment

Jiao, Shouguo; Li, Jingxiang; Liu, Binbin; Yang, Ming; Xiu, Jiangli; Qu, Daokui

doi:10.1042/bsr20181176

Cited by 8 publications

(9 citation statements)

References 51 publications

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“…In the NP tissue, NP cells are the primary cells which are responsible for matrix biosynthesis and degeneration [17]. Previous studies have reached a consensus that disc NP cell apoptosis plays an implicate role in initiating and accelerating the disc degeneration process [18][19][20][21][22][23][24][25]. Additionally, several studies found that a high-glucose culture facilitates disc cell apoptosis [6,11,14,26].…”

Section: Introductionmentioning

confidence: 99%

Melatonin Suppresses Apoptosis of Nucleus Pulposus Cells through Inhibiting Autophagy via the PI3K/Akt Pathway in a High-Glucose Culture

Wang

Xue

et al. 2021

BioMed Research International

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Diabetes mellitus- (DM-) associated hyperglycemia promotes apoptosis of disc nucleus pulposus (NP) cells, which is a contributor to intervertebral disc degeneration (IDD). Melatonin is able to protect against cell apoptosis. However, its effects on apoptosis of NP cell in a high-glucose culture remain unclear. The purpose of the present study was to investigate the effects and molecular mechanism of melatonin on NP cell apoptosis in a high-glucose culture. NP cells were cultured in the baseline medium supplemented with a high-glucose concentration (0.2 M) for 3 days. The control cells were only cultured in the baseline medium. Additionally, the pharmaceutical inhibitor LY294002 was added along with the culture medium to investigate the possible role of the PI3K/Akt pathway. Apoptosis, autophagy, and activity of the PI3K/Akt pathway of NP cells among these groups were evaluated. Compared with the control NP cells, high glucose significantly increased cell apoptosis ratio and caspase-3/caspase-9 activity and decreased mRNA expression of Bcl-2, whereas it increased mRNA or protein expression of Bax, caspase-3, cleaved caspase-3, cleaved PARP, and autophagy-related molecules (Atg3, Atg5, Beclin-1, and LC3-II) and decreased protein expression of p-Akt compared with the control cells. Additionally, melatonin partly inhibited the effects of high glucose on those parameters of cell apoptosis, autophagy, and activation of PI3K/Akt. In conclusion, melatonin attenuates apoptosis of NP cells through inhibiting the excessive autophagy via the PI3K/Akt pathway in a high-glucose culture. This study provides new theoretical basis of the protective effects of melatonin against disc degeneration in a DM patient.

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Section: Introductionmentioning

confidence: 99%

Melatonin Suppresses Apoptosis of Nucleus Pulposus Cells through Inhibiting Autophagy via the PI3K/Akt Pathway in a High-Glucose Culture

Wang

Xue

et al. 2021

BioMed Research International

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“…A large of studies shown that the degeneration mainly displays as a large number of the nucleus pulposus cell apoptosis and thus nucleus pulposus cells apoptosis plays a crucial role in IVDD [7,8]. TNF-α is a key proinflammatory cytokine and could induce the apoptosis of nucleus pulposus cells [9].…”

Section: Introductionmentioning

confidence: 99%

Knockdown of miR-660 protects nucleus pulposus cells from TNF-a-induced apoptosis by targeting serum amyloid A1

et al. 2020

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Background: Intervertebral disc degeneration (IVDD) is a well-known cause of lower back pain, which is induced by multiple factors including increased apoptosis and decreased survival of nucleus pulposus cells. In this study, we evaluate the effect and potential mechanism of miR-660 on the nucleus pulposus cells apoptosis induced by TNF-α. Methods: First, we collected tissue of nucleus pulposus from IVDD and healthy controls. General characteristic of the IVDD and healthy control was also collected. And, we also collected nucleus pulposus cells that stimulated by TNF-α or control. miRNA microarray was performed to identify the differentially expressed miRNAs. Apoptosis rate and miR-660 relative expression was measured after stimulated with different concentration of TNF-α to identify the optimal concentration of TNF-α. Second, we successfully constructed antigomiR-660 to block the miR-660 expression in nucleus pulposus cells and then stimulated with TNF-α (100 ng/ml, 12 h). The apoptosis rates and relative protein expression were then measured again. The target association between miR-660 and SAA1 was confirmed by dual-luciferase reporter. Results: There was no significant difference between the age (IVDD: 39 ± 10 years, healthy controls: 36 ± 7 years), BMI and sex between IVDD and healthy controls. Microarray analysis found that miR-660 was significantly upregulated in IVDD and TNF-α treated groups, which was further identified by PCR. We found that the rate of apoptosis and miR-660 expression increased with TNF-α concentration increased. Finally, TNF-a with 100 ng/ml was used for further experiment. Compared with TNF-α group, TNF-α + antigomiR-660 could significantly downregulated the apoptosis rate and relative protein (c-Caspase3 and c-Caspase7). Dual-luciferase reporter revealed that miR-660 could directly binding to the SAA1 at 80-87 sites. Compared with TNF-α alone group, TNF-α + antigomiR-660 significantly up-regulated the SAA1 expression (P < 0.05). Conclusion: These results indicated that knockdown of miR-660 protected the nucleus pulposus from apoptosis that induced TNF-α via up-regulation of SAA1. Further studies should focus on the role of miR-660 in protecting IVDD in vivo.

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“…Li et al showed that in primary human corneal epithelial cells, hyperosmolality conditions reduced expression of the nuclear transcriptional factor (Nrf2) which is responsible for reduction in ROS levels and increasing the total antioxidant level via regulation of antioxidant gene expression, such as NAD(P)H quinoneoxido reductase 1 (NQO1), glutathione peroxidase (GPx) and glutamate cysteine ligase (GCLC) [ 113 ]. Similarly, another study showed that hyperosmolarity culture enhanced ROS production and decreased the total SOD activity compared with the control [ 114 ]; however, on the other hand, some studies have revealed that melatonin can regulate the expression of antioxidant enzymes through the activation of Nrf2 and its downstream genes such as HO-1, CAT, SOD and GSTM1 [ 28 ]. Towards this, Feng et al showed that melatonin considerably increased the enzyme activity and protein expression of SOD, CAT and GSH-Px, which are the main antioxidant enzymes in cells and are responsible for converting superoxide radicals into water (SOD1 and SOD2: dismutase, the superoxide radical, into hydrogen peroxide and oxygen, and then GSH-Px and CAT convert the hydrogen peroxide to water) [ 94 ].…”

Section: Discussionmentioning

confidence: 99%

Exogenous Melatonin Ameliorates the Negative Effect of Osmotic Stress in Human and Bovine Ovarian Stromal Cells

2022

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Ovarian tissue cryopreservation transplantation (OTCT) is the most flexible option to preserve fertility in women and children with cancer. However, OTCT is associated with follicle loss and an accompanying short lifespan of the grafts. Cryopreservation-induced damage could be due to cryoprotective agent (CPA) toxicity and osmotic shock. Therefore, one way to avoid this damage is to maintain the cell volume within osmotic tolerance limits (OTLs). Here, we aimed to determine, for the first time, the OTLs of ovarian stromal cells (OSCs) and their relationship with reactive oxygen species (ROS) and mitochondrial respiratory chain activity (MRCA) of OSCs. We evaluated the effect of an optimal dose of melatonin on OTLs, viability, MRCA, ROS and total antioxidant capacity (TAC) of both human and bovine OSCs in plated and suspended cells. The OTLs of OSCs were between 200 and 375 mOsm/kg in bovine and between 150 and 500 mOsm/kg in human. Melatonin expands OTLs of OSCs. Furthermore, melatonin significantly reduced ROS and improved TAC, MRCA and viability. Due to the narrow osmotic window of OSCs, it is important to optimize the current protocols of OTCT to maintain enough alive stromal cells, which are necessary for follicle development and graft longevity. The addition of melatonin is a promising strategy for improved cryopreservation media.

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Nucleus pulposus cell apoptosis is attenuated by CDMP-2 through regulating oxidative damage under the hyperosmotic environment

Cited by 8 publications

References 51 publications

Melatonin Suppresses Apoptosis of Nucleus Pulposus Cells through Inhibiting Autophagy via the PI3K/Akt Pathway in a High-Glucose Culture

Melatonin Suppresses Apoptosis of Nucleus Pulposus Cells through Inhibiting Autophagy via the PI3K/Akt Pathway in a High-Glucose Culture

Knockdown of miR-660 protects nucleus pulposus cells from TNF-a-induced apoptosis by targeting serum amyloid A1

Exogenous Melatonin Ameliorates the Negative Effect of Osmotic Stress in Human and Bovine Ovarian Stromal Cells

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