scholarly journals Aquaporin-3 Attenuates Oxidative Stress-Induced Nucleus Pulposus Cell Apoptosis Through Regulating the P38 MAPK Pathway

2018 ◽  
Vol 50 (5) ◽  
pp. 1687-1697 ◽  
Author(s):  
Yichun Xu ◽  
Hui Yao ◽  
Qiyou Wang ◽  
Wenbin Xu ◽  
Kaihua Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Oxidative Damage ◽  
P38 Mapk ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Mapk Pathway ◽  
Aquaporin 3 ◽  
P38 Mapk Pathway ◽  
Intracellular Ros ◽  
Cellular Apoptosis

Background/Aims: Previous studies have shown that oxidative damage is a main contributor to disc nucleus pulposus (NP) cell apoptosis. Aquaporin-3 (AQP-3) facilitates reactive oxygen species (ROS) scavenging and thus alleviates oxidative injury in other cells. This study aims to investigate the role and mechanism of AQP-3 in regulating NP cell apoptosis under oxidative damage. Methods: Rat NP cells were treated with H2O2 for 48 hours, while control NP cells were free of H2O2. Recombinant AQP-3 lentiviral vectors were used to investigate the effect of enhanced AQP-3 expression levels in NP cells. NP cell apoptosis was assessed by flow cytometry, caspase-3 activity, gene expression of apoptosis-related molecules (Bax, Bcl-2 and caspase-3), and protein expression of cellular apoptosis markers (cleaved PARP and cleaved caspase-3). Additionally, intracellular ROS content and activity of the p38 MAPK pathway were evaluated. Results: Compared with the control NP cells, oxidative damage in the treatment cells significantly increased cell apoptosis ratios and caspase-3 activity, upregulated gene expression of Bax and caspase-3, downregulated gene expression of Bcl-2, and increased protein expression of cleaved PARP and cleaved caspase-3, as well as increased intracellular ROS content and activity of the p38 MAPK pathway. However, AQP-3 overexpression partly alleviated cell apoptosis, decreased intracellular ROS content, and inhibited the p38 MAPK pathway in NP cells under oxidative damage. Conclusion: Oxidative damage can significantly downregulate AQP-3 expression. Enhancing AQP-3 expression in NP cells partly attenuates cellular apoptosis through regulating the p38 MAPK pathway under oxidative damage.

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.

scholarly journals Osteogenic protein-1 attenuates apoptosis and enhances matrix synthesis of nucleus pulposus cells under high magnitude compression though inhibiting the p38 MAPK pathway

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Haolin Fang ◽  
Xianzhou Li ◽  
Haiming Shen ◽  
Buwei Sun ◽  
Haijun Teng ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
P38 Mapk ◽  
Disc Degeneration ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Mapk Pathway ◽  
High Magnitude ◽  
P38 Mapk Pathway ◽  
Regulated Expression ◽  
Osteogenic Protein

Disc degeneration is correlated with mechanical load. Osteogenic protein-1 (OP-1) is potential to regenerate degenerative disc. To investigate whether OP-1 can protect against high magitude compression-induced nucleus pulposus (NP) cell apoptosis and NP matrix catabolism, and its potential mechanism; porcine discs were cultured in a bioreactor and compressed at a relatively high-magnitude mechanical compression (1.3 MPa at a frequency of 1.0 Hz for 2 h once per day) for 7 days. OP-1 was added along with the culture medium to investigate the protective effects of OP-1. NP cell apoptosis and matrix biosynthesis were evaluated. Additionally, activity of the p38 MAPK pathway is also analyzed. Compared with the control group, high magnitude compression significantly promoted NP cell apoptosis and decreased NP matrix biosynthesis, reflected by the increase in the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells and caspase-3 activity, the up-regulated expression of Bax and caspase-3 mRNA and down-regulated expression of Bcl-2 mRNA, and the decreased Alcian Blue staining intensity and expression of matrix proteins (aggrecan and collagen II). However, OP-1 addition partly attenuated the effects of high magnitude compression on NP cell apoptosis and NP matrix biosynthesis. Further analysis showed that inhibition of the p38 MAPK pathway partly participated in this process. OP-1 can attenuate high magnitude compression-induced NP cell apoptosis and promoted NP matrix biosynthesis, and inhibition of the p38 MAPK pathway may participate in this regulatory process. The present study provides that OP-1 may be efficient in retarding mechanical overloading-exacerbated disc degeneration.

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.

Carbon monoxide alleviates ethanol-induced oxidative damage and inflammatory stress through activating p38 MAPK pathway

2013 ◽  
Vol 273 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Yanyan Li ◽  
Chao Gao ◽  
Yanru Shi ◽  
Yuhan Tang ◽  
Liang Liu ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Oxidative Damage ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Inflammatory Stress ◽  
P38 Mapk Pathway

scholarly journals Activin Inhibits the Human Pit-1 Gene Promoter through the p38 Kinase Pathway in a Smad-Independent Manner

Endocrinology ◽  
2006 ◽  
Vol 147 (9) ◽  
pp. 4351-4362 ◽  
Author(s):  
Chantal de Guise ◽  
Annie Lacerte ◽  
Shahrzad Rafiei ◽  
Rachel Reynaud ◽  
Melanie Roy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pituitary Gland ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Critical Role ◽  
Gene Promoter ◽  
Negative Regulator ◽  
P38 Kinase ◽  
P38 Mapk Pathway ◽  
Lactotrope Cells

The pituitary transcription factor Pit-1 regulates hormonal production from the anterior pituitary gland. However, the mechanisms by which Pit-1 gene expression is regulated in humans are poorly understood. Activin, a member of the TGFβ superfamily, acts as a negative regulator of cell growth and prolactin gene expression in lactotrope cells. In this study, we show that activin negatively regulates the human Pit-1 gene promoter. We defined a 117-bp element within the Pit-1 promoter that is sufficient to relay these inhibitory effects. We further investigated the signaling pathways that mediate activin-induced inhibition of Pit-1 gene promoter in pituitary lactotrope cells. We found that the activin effects on Pit-1 gene regulation are Smad independent and require the p38 MAPK pathway. Specifically, blocking p38 kinase activity reverses activin-mediated inhibition of the Pit-1 gene promoter. Together, our results highlight the p38 MAPK pathway as a key regulator of activin function in pituitary lactotrope cells and further emphasizes the critical role played by activin in regulating hormonal production in the pituitary gland.

scholarly journals Progesterone induces cell apoptosis via the CACNA2D3/Ca2+/p38 MAPK pathway in endometrial cancer

2019 ◽  
Author(s):  
Xiangnan Kong ◽  
Min Li ◽  
Kai Shao ◽  
Yinrong Yang ◽  
Qian Wang ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
P38 Mapk ◽  
Cell Apoptosis ◽  
Mapk Pathway ◽  
P38 Mapk Pathway
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