scholarly journals Apocynin Attenuates Cobalt Chloride-Induced Pheochromocytoma Cell Apoptosis by Inhibiting P38-MAPK/Caspase-3 Pathway

2018 ◽  
Vol 48 (1) ◽  
pp. 208-214 ◽  
Author(s):  
Jie  Liu ◽  
Yuzhang Zhu ◽  
Shipiao Chen ◽  
Bin Shen ◽  
Fang Yu ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Pc12 Cell ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Cobalt Chloride ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Oxidase Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay

Background/Aims: Apocynin, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, has been identified as a potential neuroprotectant. In this study, we aimed to investigate the protective effect of apocynin against cobalt chloride (CoCl2)-induced pheochromocytoma (PC12) cell apoptosis. Methods: The PC12 cell culture was pretreated with apocynin and/or SB203580 (p38 mitogen-activated protein kinase [p38-MAPK] inhibitor) at different time points prior to CoCl2 incubation. The cell viability, apoptosis rate, DAN damage, and antioxidant activity were detected using cell counting kit-8 (CCK-8), flow cytometry, enzyme-linked immunosorbent assay (ELISA), and comet assay respectively. The protein and mRNA expressions of p38-MAPK and caspase-3 in the cells were measured by qRT-PCR and Western blotting. Results: Apocynin inhibited CoCl2-mediated apoptosis, reduced oxidative stress, and down-regulated the expression of p38-MAPK and caspase-3. Conclusions: Our findings show that apocynin attenuated CoCl2-induced apoptosis by potently restraining p38-MAPK-caspase-3 signaling pathway in PC12 cells, suggesting that apocynin may be a potent prophylactic reagent against CoCl2-mediated PC12 cell apoptosis.

scholarly journals Acetylcholine Attenuated TNF-α-Induced Apoptosis in H9c2 Cells: Role of Calpain and the p38-MAPK Pathway

2015 ◽  
Vol 36 (5) ◽  
pp. 1877-1889 ◽  
Author(s):  
Ming Zhao ◽  
Yang Yang ◽  
Xueyuan Bi ◽  
Xiaojiang Yu ◽  
Hanghuan Jia ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Inflammatory Factors ◽  
Calpain Inhibitor ◽  
Mapk Phosphorylation ◽  
Tnf Α ◽  
Expression And Activity

Background: Previous studies have shown that inflammation is associated with excessive activation of calpains. Acetylcholine (ACh) has been reported to inhibit pro-inflammatory cytokine release and protect against cardiomyocyte injury. However, there is no direct evidence regarding whether ACh can regulate calpains to exert cardioprotection. To this end, we investigated the effect of ACh on tumour necrosis factor alpha (TNF-α)-induced cardiomyocyte injury and further explored the underlying mechanism. Methods: Flow cytometry and transmission electron microscopy were performed to evaluate apoptosis and cellular ultrastructure. Western blotting was performed to assess changes in protein expression. siRNA was employed to silence specific proteins. Results: TNF-α treatment increased the expression of cleaved caspase-3, calpain-1 and p38-mitogen-activated protein kinase (p38-MAPK). The calpain inhibitor PD150606 and the p38-MAPK inhibitor SB203580 inhibited apoptosis induced by TNF-α. Moreover, SB203580 decreased the expression and activity of calpain-1, possibly related to the up-regulation of calpastatin. ACh significantly inhibited TNF-α-induced cell apoptosis, as evidenced by decreases in caspase-3 cleavage, p38-MAPK phosphorylation, and calpain-1 expression and activity as well as increases in calpastatin expression. These beneficial effects of ACh were abolished by atropine or M2AChR siRNA. Conclusion: Our results suggest that ACh ameliorated TNF-α-induced calpain activation by decreasing p38-MAPK phosphorylation and enhancing calpastatin expression, indicating that calpain may be an important link between inflammatory factors and myocardial cell apoptosis.

scholarly journals MiR-140-3p inhibits the cell viability and promotes apoptosis of synovial fibroblasts in rheumatoid arthritis through targeting sirtuin 3

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Beibei Zu ◽  
Lin Liu ◽  
Jingya Wang ◽  
Meirong Li ◽  
Junxia Yang
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Pearson Correlation ◽  
Fibrous Tissue ◽  
Synovial Fibroblasts ◽  
Cell Counting ◽  
Sirtuin 3 ◽  
Fibrous Tissues

Abstract Background Synovial fibroblasts (SFs) with the abnormal expressions of miRNAs are the key regulator in rheumatoid arthritis (RA). Low-expressed miR-140-3p was found in RA tissues. Therefore, we attempted to investigate the effect of miR-140-3p on SFs of RA. Methods RA and normal synovial fibrous tissue were gathered. The targets of miR-140-3p were found by bioinformatics and luciferase analysis. Correlation between the expressions of miR-140-3p with sirtuin 3 (SIRT3) was analyzed by Pearson correlation analysis. After transfection, cell viability and apoptosis were detected by cell counting kit-8 and flow cytometry. The expressions of miR-140-3p, SIRT3, Ki67, Bcl-2, Bax, and cleaved Caspase-3 were detected by RT-qPCR or western blot. Results Low expression of miR-140-3p and high expression of SIRT3 were found in RA synovial fibrous tissues. SIRT3 was a target of miR-140-3p. SIRT3 expression was negatively correlated to the expression of miR-140-3p. MiR-140-3p mimic inhibited the MH7A cell viability and the expressions of SIRT3, Ki67, and Bcl-2 and promoted the cell apoptosis and the expressions of Bax and cleaved Caspase-3; miR-140-3p inhibitor showed an opposite effect to miR-140-3p mimic on MH7A cells. SIRT3 overexpression not only promoted the cell viability and inhibited cell apoptosis of MH7A cells but also reversed the effect of miR-140-3p mimic had on MH7A cells. Conclusions The results in this study revealed that miR-140-3p could inhibit cell viability and promote apoptosis of SFs in RA through targeting SIRT3.

scholarly journals Qingxin Kaiqiao Fang Inhibits Aβ25-35-Induced Apoptosis in Primary Cultured Rat Hippocampal Neuronal Cells via the p38 MAPK Pathway: An Experimental Validation and Network Pharmacology Study

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Tian-Qi Wang ◽  
Xiao-Xiao Lai ◽  
Lu-Ting Xu ◽  
Yan Shen ◽  
Jian-Wei Lin ◽  
...  
Keyword(s):  
Cell Viability ◽  
P38 Mapk ◽  
Caspase 3 ◽  
Mapk Pathway ◽  
Neuronal Cells ◽  
Neuronal Morphology ◽  
Cell Counting ◽  
Network Pharmacology ◽  
Expression Levels ◽  
P38 Mapk Pathway

Qingxin kaiqiao fang (QKF), a traditional Chinese medicine compound, has been applied to treat Alzheimer’s disease (AD) for many years and has exhibited remarkable effects. However, the underlying mechanism is still not explicit. The current study aims to investigate whether QKF exerts an antiapoptotic role through the p38 MAPK pathway in the course of AD. Network pharmacology analysis was applied to study the effective components, possible therapeutic targets, and AD-related pathway of QKF. Further, the AD cell model was established using amyloid-beta (Aβ)25-35 peptide and primary hippocampal neuronal cells extracted from newborn Sprague-Dawley rats. Microtubule-associated protein-2 (MAP-2) imaging was used to detect the morphology of hippocampal neurons. Western blot (WB) analysis was applied to detect the protein expression levels of p38 MAPK, p-p38 MAPK, Bcl-2, Bax, caspase-3, and cleaved caspase-3. Cell viability and apoptosis were determined using cell counting kit-8 (CCK-8) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, respectively. SB203580 and U46619 were used to detect changes in cell morphology, cell viability, and apoptosis upon inhibiting or activating p38 MAPK. Our present work showed that QKF protects hippocampal neuronal morphology, enhances cell viability, and reduces the number of TUNEL-positive cells. In addition, our results showed that QKF increased the expression levels of antiapoptotic proteins and decreased the expression of proapoptotic proteins. QKF at 25 mg·mL−1 best inhibited neuronal apoptosis among the three doses of QKF by suppressing p38 MAPK activity. Collectively, QKF plays an antiapoptotic role via the p38 MAPK pathway.

scholarly journals Bakuchiol Suppresses Inflammatory Responses Via the Downregulation of the p38 MAPK/ERK Signaling Pathway

2019 ◽  
Vol 20 (14) ◽  
pp. 3574 ◽  
Author(s):  
Hye-Sun Lim ◽  
Yu Jin Kim ◽  
Bu-Yeo Kim ◽  
Soo-Jin Jeong
Keyword(s):  
Mrna Expression ◽  
P38 Mapk ◽  
Inflammatory Responses ◽  
Mitogen Activated Protein Kinase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mice Model ◽  
Tnf Α ◽  
Cox 2

The purpose of the present study was to evaluate the effects of bakuchiol on the inflammatory response and to identify the molecular mechanism of the inflammatory effects in a lipopolysaccharide (LPS)-stimulated BV-2 mouse microglial cell line and mice model. The production of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay. The mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-6 was measured using reverse transcription–polymerase chain reaction analysis. Mitogen-activated protein kinase (MAPK) phosphorylation was determined by western blot analysis. In vitro experiments, bakuchiol significantly suppressed the production of PGE2 and IL-6 in LPS-stimulated BV-2 cells, without causing cytotoxicity. In parallel, bakuchiol significantly inhibited the LPS-stimulated expression of iNOS, COX-2, and IL-6 in BV-2 cells. However, bakuchiol had no effect on the LPS-stimulated production and mRNA expression of TNF-α or on LPS-stimulated c-Jun NH2-terminal kinase phosphorylation. In contrast, p38 MAPK and extracellular signal-regulated kinase (ERK) phosphorylation were inhibited by bakuchiol. In vivo experiments, Bakuchiol reduced microglial activation in the hippocampus and cortex tissue of LPS-injected mice. Bakuchiol significantly suppressed LPS-injected production of TNF-α and IL-6 in serum. These results indicate that the anti-neuroinflammatory effects of bakuchiol in activated microglia are mainly regulated by the inhibition of the p38 MAPK and ERK pathways. We suggest that bakuchiol may be beneficial for various neuroinflammatory diseases.

scholarly journals Endoplasmic reticulum stress regulates cell injury in lipopolysaccharide-induced nerve cells

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052094976
Author(s):  
Min Li ◽  
Ying Zhang ◽  
Jixing Wang
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Viability ◽  
Er Stress ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Cell Injury ◽  
Cell Counting ◽  
Tunel Staining ◽  
Dependent Manner ◽  
Stress Markers

Objective Sepsis-associated encephalopathy (SAE) is a common complication of sepsis, and excessive endoplasmic reticulum (ER) stress is closely correlated with the cell injury caused by sepsis. This study aimed to analyze the possible role of ER stress in SAE cell models. Methods PC12 and MES23.5 cells were treated with increasing concentrations of lipopolysaccharides (LPS). The Cell Counting Kit-8 assay was used to detect cell viability and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed to assess cell apoptosis. In addition, the protein expression levels of ER stress markers [GRP78, CHOP, inositol-requiring enzyme 1 (IRE1), and PKR-like ER kinase (PERK)] and apoptosis-related proteins (Bax, Bcl-2, caspase-3, and cleaved caspase-3) were analyzed using western blotting. Results LPS treatment activated ER stress markers in both the PC12 and MES23.5 cells. The overexpression of GRP78 significantly reduced cell viability and enhanced cell apoptosis in a time-dependent manner. An ER stress inhibitor, 4-PBA, significantly enhanced cell viability and inhibited the cell apoptosis induced by LPS. Therefore, an enhanced unfolded protein response (UPR) and UPR suppression may regulate cell apoptosis. Conclusions UPR was shown to be involved in regulating LPS-induced neuron injury. UPR could be a potential therapeutic target in SAE.

Cytosolic phospholipase A2-α is an early apoptotic activator in PEDF-induced endothelial cell apoptosis

2009 ◽  
Vol 296 (2) ◽  
pp. C273-C284 ◽  
Author(s):  
Tsung-Chuan Ho ◽  
Show-Li Chen ◽  
Yuh-Cheng Yang ◽  
Tzu-Hsiu Lo ◽  
Jui-Wen Hsieh ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
P38 Mapk ◽  
Cell Apoptosis ◽  
Nuclear Translocation ◽  
Mitogen Activated Protein Kinase ◽  
Endothelial Cell Apoptosis ◽  
P53 Expression ◽  
Ppar Γ

Pigment epithelium-derived factor (PEDF) is an intrinsic antiangiogenic factor and a potential therapeutic agent. Previously, we discovered the mechanism of PEDF-induced apoptosis of human umbilical vein endothelial cells (HUVECs) as sequential induction/activation of p38 mitogen-activated protein kinase (MAPK), peroxisome proliferator-activated receptor gamma (PPAR-γ), and p53. In the present study, we investigated the signaling role of cytosolic calcium-dependent phospholipase A2-α (cPLA2-α) to bridge p38 MAPK and PPAR-γ activation. PEDF induced cPLA2-α activation in HUVECs and in endothelial cells in chemical burn-induced vessels on mouse cornea. The cPLA2-α activation is evident from the phosphorylation and nuclear translocation of cPLA2-α as well as arachidonic acid release and the cleavage of PED6, a synthetic PLA2 substrate. Such activation can be abolished by p38 MAPK inhibitor. The PEDF-induced PPAR-γ activation, p53 expression, caspase-3 activity, and apoptosis can be abolished by both cPLA2 inhibitor and small interfering RNA targeting cPLA2-α. Our observation not only establishes the signaling role of cPLA2-α but also for the first time demonstrates the sequential activation of p38 MAPK, cPLA2-α, PPAR-γ, and p53 as the mechanism of PEDF-induced endothelial cell apoptosis.

scholarly journals The Role of Thymoquinone in Mitigating Carbon Tetrachloride-Induced Hepatocellular Carcinoma in Rats: Targeting the CHOP-1/JNK/P38 MAPK, NFκB/TNF-α/IL-10, and Bax/Bcl-2/Caspase-3 Signalling Pathways

2021 ◽  
Vol 69 (1) ◽  
pp. 1-9
Author(s):  
Rania Elsayed Hussein ◽  
Laila Ahmed Rashed ◽  
Basma Emad Aboulhoda ◽  
Ghada Mahmoud Abdelaziz ◽  
Ebtehal Gamal Abdelhady ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
P38 Mapk ◽  
Caspase 3 ◽  
B Cell Lymphoma ◽  
Mitogen Activated Protein Kinase ◽  
Lipid Peroxidation Product ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Bax Gene

The present study was conducted to evaluate the effect of thymoquinone (TQ) on hepatocellular carcinoma (HCC) in rats. Our study has reported that TQ treatment of experimentally-induced HCC results in the up-regulation of the Jun-N-terminal kinase and p38 mitogen activated protein kinase pathway (JNK/p38 MAPK) and the enhancement of anti-inflammatory, anti-oxidant, and pro-apoptotic machineries. TQ resulted in a significant decrease in the levels of nuclear factor kappa-light-chain-enhancer of activated B-cells (NFκB), tumor necrosis factor-α (TNF-α), and a significant increase in the anti-inflammatory interleukin-10 (IL-10). The pro-apoptotic effect of TQ was demonstrated through stimulating the apoptotic Bcl-2-associated X (Bax) gene and inhibiting the anti-apoptotic B-cell lymphoma 2 (Bcl-2) gene together with increasing the level of caspase 3 and up-regulating the C/EBP homologous protein (CHOP-1) gene expression. TQ treatment also enhanced the activity of the ROS scavenger, superoxide dismutase (SOD), and decreased the level of the lipid peroxidation product malondialdehyde (MDA). TQ-dependent suppression of HCC was associated with the up-regulation of JNK/p38 MAPK, enhanced CHOP-1 expression, and subsequently increased Bax gene expression.

scholarly journals Protective Effects of Astragalus Polysaccharide on Sepsis-Induced Acute Kidney Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Jie Sun ◽  
Shanzhai Wei ◽  
Yilai Zhang ◽  
Jia Li
Keyword(s):  
Caspase 3 ◽  
Morphological Changes ◽  
Kidney Injury ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
In Vitro Experiments ◽  
Caspase 9 ◽  
Astragalus Polysaccharide ◽  
Tnf Α

Objective. To explore the protective roles of Astragalus polysaccharide (APS) on acute renal injury (AKI) induced by sepsis. Methods. Firstly, an animal model of sepsis-induced AKI was established by injecting lipopolysaccharide (LPS) into mice. The mice were pretreated with an intraperitoneal injection of 1, 3, and 5 mg/(kg·d) APS for 3 consecutive days. The severity of kidney injury was then scored by histopathological analysis, and the concentrations of serum urea nitrogen (BUN) and serum creatinine (SCr) and the levels of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) were determined as well. In in vitro experiments, lipopolysaccharide (LPS) was used to induce HK-2 cell injury to establish a sepsis-induced AKI cell model, and the cell counting kit-8 (CCK-8) method was performed to determine the cytotoxicity and appropriate experimental concentration of APS. Then, cells were divided into the control, LPS, and APS+LPS groups. Cell apoptosis and inflammation-related TNF-α, IL-1β, IL-6, and IL-8 were determined by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The microscope was used to observe the morphological changes of cells, and the cell migration ability was measured by wound healing assay. RT-qPCR and Western blot assay were used to determine the mRNA and protein levels of apoptosis-related factors including caspase-3, caspase-9, Bax, and Bcl-2; endoplasmic reticulum stress- (ERS-) related biomarkers including C/EBP homologous protein (CHOP) and glucose-regulated protein78 (GRP78); and epithelial-mesenchymal transition- (EMT-) related biomarkers including E-cadherin, Snail, α-smooth muscle actin (α-SMΑ), and Vimentin. Results. In vivo experiments in mice showed that APS can reverse LPS-induced kidney damage in a concentration-dependent manner ( P < 0.05 ); the concentrations of BUN and Scr were increased (all P < 0.05 ); similarly, the levels of TNF-α and IL-1β were increased as well (all P < 0.05 ). In in vitro experiments, the results showed that LPS can significantly cause HK-2 cell damage and induce apoptosis, inflammation, ERS, and EMT. When APS concentration was in the range of 0-200 μg/mL, it had no cytotoxicity in HK-2 cells, and 100 μg/mL APS pretreatment could significantly mitigate the decrease of cell activity induced by LPS ( P < 0.05 ). Compared with the LPS group, APS pretreatment could inhibit the expression of inflammatory factors including TNF-α, IL-1 β, IL-6, and IL-8 (all P < 0.05 ), reducing the number of apoptotic cells ( P < 0.05 ), suppressing the expression of caspase-3, caspase-9, and Bax, but upregulating the expression levels of Bcl-2. In ERS, APS pretreatment inhibited LPS-induced upregulation of CHOP and GRP78. Moreover, in EMT, APS pretreatment could inhibit the morphological changes of cells, downregulate the migration, decrease the expression of EMT biomarkers, and inhibit the process of EMT. Conclusion. APS could alleviate sepsis-induced AKI by regulating inflammation, apoptosis, ERS, and EMT.

scholarly journals Skullcapflavone I protects cardiomyocytes from hypoxia-caused injury through up-regulation of lincRNA-ROR

2019 ◽  
Vol 33 ◽  
pp. 205873841985753 ◽  
Author(s):  
Zhenxiao Zhang ◽  
Hui Li ◽  
Mingyang Liu ◽  
Jianshuai He ◽  
Xiaotian Zhang ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Cell Injury ◽  
Mitogen Activated Protein Kinase ◽  
Cell Counting ◽  
H9c2 Cell ◽  
Erk Pathway ◽  
H9c2 Cells ◽  
Scutellaria Baicalensis Georgi ◽  
Protein Levels

Myocardial infarction (MI) is a serious heart disease in which cardiomyocytes are damaged, caused by hypoxia. This study explored the possible protective activity of Skullcapflavone I (SF I), a flavonoid isolated from the root of Scutellaria baicalensis Georgi, on hypoxia-stimulated cardiomyocytes cell injury in vitro. Viability and apoptosis of H9c2 cells and primary cardiomyocytes were tested using cell counting kit–8 (CCK-8) assay and Guava Nexin Reagent, respectively. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to measure the long non-coding RNA regulator of reprogramming (lincRNA-ROR) expression. si-ROR was transfected to knockdown lincRNA-ROR. Western blotting was conducted to assess the protein levels of key molecules related to cell proliferation, apoptosis, and mitogen-activated protein kinase/extracellular signal–regulated kinase (MEK/ERK) pathway. We discovered that hypoxia stimulation obviously reduced H9c2 cell and primary cardiomyocytes’ viability and proliferation, but promoted cell apoptosis. SF I treatment mitigated the cell viability and proliferation inhibition, as well as cell apoptosis caused by hypoxia. Moreover, SF I promoted the hypoxia-caused up-regulation of lincRNA-ROR in H9c2 cells and primary cardiomyocytes. Knockdown of lincRNA-ROR reversed the influence of SF I on hypoxia-stimulated H9c2 cells and primary cardiomyocytes. Besides, SF I activated MEK/ERK pathway in H9c2 cells and primary cardiomyocytes via up-regulating lincRNA-ROR. To sum up, our research verified the beneficial activity of SF I on hypoxia-caused cardiomyocytes injury. SF I protected cardiomyocytes from hypoxia-caused injury through up-regulation of lincRNA-ROR and activation of MEK/ERK pathway.

scholarly journals Mechano growth factor attenuates mechanical overload-induced nucleus pulposus cell apoptosis through inhibiting the p38 MAPK pathway

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Qing Xu ◽  
Haolin Fang ◽  
Liang Zhao ◽  
Cunxin Zhang ◽  
Luo Zhang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Expression ◽  
Nucleus Pulposus ◽  
P38 Mapk ◽  
Disc Degeneration ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Mapk Pathway ◽  
P38 Mapk Pathway ◽  
Mechanical Overload

Abstract Mechanical overload is a risk factor of disc degeneration. It can induce disc degeneration through mediating cell apoptosis. Mechano growth factor (MGF) has been reported to inhibit mechanical overload-induced apoptosis of chondrocytes. The present study is aimed to investigate whether MGF can attenuate mechanical overload-induced nucleus pulposus (NP) cell apoptosis and the possible signaling transduction pathway. Rat NP cells were cultured and subjected to mechanical overload for 7 days. The control NP cells did not experience mechanical load. The exogenous MGF peptide was added into the culture medium to investigate its protective effects. NP cell apoptosis ratio, caspase-3 activity, gene expression of Bcl-2, Bax and caspase-3, protein expression of cleaved caspase-3, cleaved PARP, Bax and Bcl-2 were analyzed to evaluate NP cell apoptosis. In addition, activity of the p38 MAPK pathway was also detected. Compared with the control NP cells, mechanical overload significantly increased NP cell apoptosis and caspase-3 activity, up-regulated gene/protein expression of pro-apoptosis molecules (i.e. Bax, caspase-3, cleaved caspase-3 and cleaved PARP) whereas down-regulated gene/protein expression of anti-apoptosis molecule (i.e. Bcl-2). However, exogenous MGF partly reversed these effects of mechanical overload on NP cell apoptosis. Further results showed that activity of the p38 MAPK pathway of NP cells cultured under mechanical overload was decreased by addition of MGF peptide. In conclusion, MGF is able to attenuate mechanical overload-induced NP cell apoptosis, and the p38 MAPK signaling pathway may be involved in this process. The present study provides that MGF supplementation may be a promising strategy to retard mechanical overload-induced disc degeneration.

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