scholarly journals Midazolam suppresses ischemia/reperfusion-induced cardiomyocyte apoptosis by inhibiting the JNK/p38 MAPK signaling pathway

2021 ◽  
Author(s):  
Weixiao Zhou ◽  
Dongjiang Cai
Keyword(s):  
Infarct Size ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Cardiomyocyte Apoptosis ◽  
Tetrazolium Chloride

Myocardial ischemia/reperfusion (I/R) injury causes irreversible injury to the heart, causing mainly acute myocardial infarction. Midazolam is a benzodiazepine commonly utilized in anesthesia and intensive care. Research has indicated midazolam plays a critical role in many diseases. However, the function of midazolam in myocardial injury induced by I/R warrants further investigation. The infarct size was examined through 2,3,5-triphenyl tetrazolium chloride (TTC) staining. The CK-MB, LDH, and AST levels were tested using commercial kits. Cell apoptosis was determined through TUNEL or flow cytometry assays. Bax, Bcl-2, cleaved caspase-3, p-p38, p38, p-JNK, JNK, p-ERK, and ERK expression was examined through western blot. In our study, midazolam was shown to suppress the infarct size and myocardial enzyme leakage in I/R rats. Additionally, midazolam was found to retard cardiomyocyte apoptosis. The JNK/p38 MAPK signaling pathway in I/R rats was inhibited by midazolam. Our findings demonstrated that in H/R-mediated H9C2 cells, anisomycin abolished the suppressive effects of midazolam on the JNK/p38 MAPK signaling pathway. Next, exploration discovered that anisomycin abolished the cytoprotective effects of midazolam on H/R-treated H9C2 cell apoptosis. Midazolam retarded I/R-induced cardiomyocyte apoptosis by inhibiting the JNK/p38 MAPK signaling pathway. These results may provide new insight into the treatment of myocardial I/R injury.

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 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 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.

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