scholarly journals Rutin Protects against Pirarubicin-Induced Cardiotoxicity through TGF-β1-p38 MAPK Signaling Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Yadi Wang ◽  
Yang Zhang ◽  
Bo Sun ◽  
Qing Tong ◽  
Liqun Ren
Keyword(s):  
Signaling Pathway ◽  
P38 Mapk ◽  
Cell Apoptosis ◽  
Dose Range ◽  
Mapk Signaling ◽  
Positive Control ◽  
Mapk Signaling Pathway ◽  
Cardioprotective Effect ◽  
Mitogen Activated Protein Kinase ◽  
Ros Generation

We investigated the potential protective effect of rutinum (RUT) against pirarubicin- (THP-) induced cardiotoxicity. THP was used to induce toxicity in rat H9c2 cardiomyoblasts. Positive control cells were pretreated with a cardioprotective agent dexrazoxane (DZR) prior to treatment with THP. Some of the cells were preincubated with RUT and a p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, both individually and in combination, prior to THP exposure. At a dose range of 30–70 μM, RUT significantly prevented THP-induced reduction in cell viability; the best cardioprotective effect was observed at a dose of 50 μM. Administration of RUT and SB203580, both individually as well as in combination, suppressed the elevation of intracellular ROS, inhibited cell apoptosis, and reversed the THP-induced upregulation of TGF-β1, p-p38 MAPK, cleaved Caspase-9, Caspase-7, and Caspase-3. A synergistic effect was observed on coadministration of RUT and SB203580. RUT protected against THP-induced cardiotoxicity by inhibition of ROS generation and suppression of cell apoptosis. The cardioprotective effect of RUT appears to be associated with the modulation of the TGF-β1-p38 MAPK signaling pathway.

scholarly journals Protective Effect of Penetratin Analogue-Tagged SOD1 on Cisplatin-Induced Nephrotoxicity through Inhibiting Oxidative Stress and JNK/p38 MAPK Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Xiao-lu Wang ◽  
Liang Wang ◽  
Fo-lan Lin ◽  
Si-si Li ◽  
Ting-xuan Lin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Membrane ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Cell Apoptosis ◽  
Mapk Signaling ◽  
Tunel Assay ◽  
Mapk Signaling Pathway ◽  
Mapk Activation ◽  
Urea Nitrogen

Copper/zinc superoxide dismutase (SOD1) can clear cisplatin- (CP-) induced excessive reactive oxygen species (ROS), but exogenous SOD1 cannot enter cells because of its low biomembrane permeability. Cell-penetrating peptides (CPPs) can rapidly cross plasma membranes. This study is aimed at identifying an efficient and stable CPP-SOD1 and investigating its effects on CP-induced nephrotoxicity. We recombined SOD1 with 14 different CPPs and purified them using an NTA-Ni2+ column. In in vitro experiments, CPPs-SOD1 cell membrane penetration ability and JNK/p38 MAPK signaling pathway were evaluated using Western blotting. ROS production, mitochondrial membrane potential (MMP), and cell apoptosis were determined using flow cytometry and immunofluorescence staining in VERO and HK-2 cells. For in vivo experiments, mice were administered PSF-SOD1 for 2 h before cotreatment with a single CP injection for an additional 4 days. Blood and kidney samples were collected for renal function assessment (creatinine, urea nitrogen, histopathology, TUNEL assay, and JNK/p38 MAPK signaling pathway). Compared with TAT-SOD1, we found that PSF-SOD1 is more efficient at crossing the cell membrane and is stable after transduction into cells. Pretreatment with PSF-SOD1 inhibited CP-induced apoptosis, ROS generation, and JNK/p38 MAPK activation and restored CP-induced MMP loss in VERO and HK-2 kidney cells. Treatment of mice with PSF-SOD1 inhibited CP-induced serum creatinine, blood urea nitrogen elevation, and JNK/p38 MAPK activation. H&E staining and TUNEL assay indicated that kidney tissue damage was alleviated following PSF-SOD1 pretreatment. Overall, PSF-SOD1 ameliorated CP-induced renal damage by partially reducing oxidative stress and cell apoptosis by regulating JNK/p38 MAPK signaling pathway and might be a better cytoprotective agent than TAT-SOD1.

scholarly journals MicroRNA-124 inhibits macrophage cell apoptosis via targeting p38/MAPK signaling pathway in atherosclerosis development

Aging ◽  
2020 ◽  
Vol 12 (13) ◽  
pp. 13005-13022
Author(s):  
Xue Liang ◽  
Lijun Wang ◽  
Manman Wang ◽  
Zhaohong Liu ◽  
Xing Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
P38 Mapk ◽  
Cell Apoptosis ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Macrophage Cell ◽  
Microrna 124 ◽  
Atherosclerosis Development

scholarly journals A long noncoding RNA binding to QKI-5 regulates germ cell apoptosis via p38 MAPK signaling pathway

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Kai Li ◽  
Shunshun Zhong ◽  
Yanyun Luo ◽  
Dingfeng Zou ◽  
Mengzhen Li ◽  
...  
Keyword(s):  
Germ Cell ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Cell Apoptosis ◽  
Rna Binding ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Germline Development ◽  
Germ Cell Apoptosis ◽  
Male Germline

Abstract Spermatogenesis is the complex process of male germline development and requires coordinated interactions by multiple gene products that undergo strict developmental regulations. Increasing evidence has suggested that a number of long noncoding RNAs (lncRNAs) may function as important regulatory molecules in various physiological and pathological processes by binding to specific proteins. Here, we identified a subset of QKI-5-binding lncRNAs in the mouse testis through the integrated analyses of RNA immunoprecipitation (RIP)-microarray and biological verification. Among the lncRNAs, we revealed that NONMMUT074098.2 (Lnc10), which was highly expressed in the spermatogonia and spermatocytes of the testis, interacted with QKI-5. Furthermore, Lnc10 depletion promoted germ cell apoptosis via the activation of p38 MAPK, whereas the simultaneous knockdown of QKI-5 could rescue the apoptotic phenotype and the activation of p38 MAPK, which were induced by the loss of Lnc10. These data indicated that the Lnc10-QKI-5 interaction was associated with the regulatory roles of QKI-5 and that the Lnc10-QKI-5 interaction inhibited the regulation of QKI-5 on the downstream p38 MAPK signaling pathway. Additionally, we functionally characterized the biological roles of Lnc10 and found that the knockdown of Lnc10 promoted the apoptosis of spermatogenic cells in vivo; this suggested that Lnc10 had an important biological role in mouse spermatogenesis. Thus, our study provides a potential strategy to investigate the biological significance of lncRNA-RBP interactions during male germline development.

scholarly journals SkQ1 Suppresses the p38 MAPK Signaling Pathway Involved in Alzheimer’s Disease-Like Pathology in OXYS Rats

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 676
Author(s):  
Natalia A. Muraleva ◽  
Natalia A. Stefanova ◽  
Nataliya G. Kolosova
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Oxys Rats ◽  
Mitogen Activated Protein Kinase ◽  
Immunofluorescent Staining ◽  
Αb Crystallin

Alzheimer’s disease (AD) is the most common type of dementia and is currently incurable, and mitogen-activated protein kinase (MAPK) p38 is implicated in the pathogenesis of AD. p38 MAPK inhibition is considered a promising strategy against AD, but there are no safe inhibitors capable of penetrating the blood–brain barrier. Earlier, we have shown that mitochondria-targeted antioxidant plastoquinonyl-decyltriphenylphosphonium (SkQ1) at nanomolar concentrations can prevent, slow down, or partially alleviate AD-like pathology in accelerated-senescence OXYS rats. Here we confirmed that dietary supplementation with SkQ1 during active progression of AD-like pathology in OXYS rats (aged 12–18 months) suppresses AD-like pathology progression, and for the first time, we showed that its effects are associated with suppression of p38 MAPK signaling pathway (MAPKsp) activity. Transcriptome analysis, western blotting, and immunofluorescent staining revealed that SkQ1 suppresses p38 MAPKsp activity in the hippocampus at the level of expression of genes involved in the p38 MAPKsp and reduces the phosphorylation of intermediate kinases (p38 MAPK and MK2) and a downstream protein (αB-crystallin). Thus, the anti-AD effects of SkQ1 are associated with improvement in the functioning of relevant signaling pathways and intracellular processes, thus making it a promising therapeutic agent for human AD.

Anti-Apoptotic Effects of Docosahexaenoic Acid in IL-1β-Induced Human Chondrosarcoma Cell Death through Involvement of the MAPK Signaling Pathway

2019 ◽  
Vol 158 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Fei Xu ◽  
Yingchun Song ◽  
Ai Guo
Keyword(s):  
Docosahexaenoic Acid ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Inflammatory Factor ◽  
Chondrosarcoma Cell ◽  
Human Chondrosarcoma

Osteoarthritis (OA) is a degenerative disease characterized by progressive articular cartilage destruction and joint marginal osteophyte formation with different degrees of synovitis. Docosahexaenoic acid (DHA) is an unsaturated fatty acid with anti-inflammatory, antioxidant, and antiapoptotic functions. In this study, the human chondrosarcoma cell line SW1353 was cultured in vitro, and an OA cell model was constructed with inflammatory factor IL-1β stimulation. After cells were treated with DHA, cell apoptosis was measured. Western blot assay was used to detect protein expression of apoptosis-related factors (Bax, Bcl-2, and cleaved caspase-3) and mitogen-activated protein kinase (MAPK) signaling pathway family members, including extracellular signal-regulated kinase (ERK), c-JUN N-terminal kinase (JNK), and p38 MAPK. Our results show that IL-1β promotes the apoptosis of SW1353 cells, increases the expression of Bax and cleaved caspase-3, and activates the MAPK signaling pathway. In contrast, DHA inhibits the expression of IL-1β, inhibits IL-1β-induced cell apoptosis, and has a certain inhibitory effect on the activation of the MAPK signaling pathway. When the MAPK signaling pathway is inhibited by its inhibitors, the effects of DHA on SW1353 cells are weakened. Thus, DHA enhances the apoptosis of SW1353 cells through the MAPK signaling pathway.

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