scholarly journals Schisandrin Protects against Norepinephrine-Induced Myocardial Hypertrophic Injury by Inhibiting the JAK2/STAT3 Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Min Yang ◽  
Xing-Can Jiang ◽  
Lei Wang ◽  
Dong-An Cui ◽  
Jing-Yan Zhang ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Cell Surface ◽  
Signaling Pathway ◽  
Surface Area ◽  
Cardiomyocyte Hypertrophy ◽  
Cell Surface Area ◽  
Apoptosis Rate ◽  
Stat3 Signaling ◽  
Hypertrophic Cell ◽  
Stat3 Signaling Pathway

Aims. Heart failure is closely associated with norepinephrine-(NE-) induced cardiomyocyte hypertrophy. Schisandrin is derived from the traditional Chinese medicine Schisandra; it has a variety of pharmacological activities, and the mechanism of schisandrin-mediated protection of the cardiovascular system is not clear. Main Methods. NE was used to establish a cardiomyocyte hypertrophy model to explore the mechanism of action of schisandrin. An MTT assay was used for cell viability; Hoechst fluorescence staining was used to observe the cell morphology and calculate the apoptosis rate. The cell surface area was measured and the protein to DNA ratio was calculated, changes in mitochondrial membrane potential were detected, and the degree of hypertrophic cell damage was evaluated. WB, QRT-PCR, and immunofluorescence were used to qualitatively, quantitatively, and quantitatively detect apoptotic proteins in the JAK2/STAT3 signaling pathway. Key Findings. In the NE-induced model, schisandrin treatment reduced the apoptosis rate of cardiomyocytes, increased the ratio of the cell surface area to cardiomyocyte protein/DNA, and also, increased the membrane potential of the mitochondria. The expression of both JAK2 and STAT3 was downregulated, and the BAX/Bcl-2 ratio was significantly reduced. In conclusion, schisandrin may protect against NE-induced cardiomyocyte hypertrophy by inhibiting the JAK2/STAT3 signaling pathway and reducing cardiomyocyte apoptosis.

RANKL downregulates cell surface CXCR6 expression through JAK2/STAT3 signaling pathway during osteoclastogenesis

2012 ◽  
Vol 429 (3-4) ◽  
pp. 156-162 ◽  
Author(s):  
Changhong Li ◽  
Jinxia Zhao ◽  
Lin Sun ◽  
Zhongqiang Yao ◽  
Rui Liu ◽  
...  
Keyword(s):  
Cell Surface ◽  
Signaling Pathway ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

Abstract 143: Caveolae Regulate PI3K/Akt/RhoA-Mediated p38 MAPK Nuclear Translocation in Leptin-Induced Cardiomyocyte Hypertrophy

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Asad Zeidan ◽  
Sabzali Javadov ◽  
Subrata Chakrabarti ◽  
Morris Karmazyn
Keyword(s):  
Cell Surface ◽  
Cardiac Hypertrophy ◽  
Surface Area ◽  
P38 Mapk ◽  
Nuclear Translocation ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Leucine Incorporation ◽  
Cell Surface Area ◽  
C3 Exoenzyme

Background : Obesity is associated with increased leptin production which may contribute to cardiac hypertrophy. However, the mechanism of leptin-induced cardiac hypertrophy remains incompletely understood. Previous studies have shown that the RhoA/ROCK/cofilin pathway and p38 MAPK but not ERK1/2 activation are major contributors to leptin-induced cardiac hypertrophy. In this study we explored the roles of caveolae and the PI3K/Akt pathway in regulating RhoA and p38 MAPK activation during leptin-induced cardiomyocyte hypertrophy. Methods and Results : Neonatal rat ventricular myocytes were cultured with 3.1 nmol/L leptin for 24 hours. Caveolae number and expression of caveolin-3 were significantly increased after leptin treatment (2 and 3 fold, respectively; p<0.01). These effects were associated with a 29% (p<0.05) increase in cell surface area and a 40% (p<0.05) increase in leucine incorporation, indicating cardiomyocyte hypertrophy. Disruption of cardiomyocyte caveolae with 5 mM methyl-beta-cyclodextrin (MβCD) significantly inhibited leptin-induced hypertrophy. RhoA was detected in caveolae fractions of a sucrose gradient after cardiomyocytes were treated with leptin for 5 min, demonstrating subcellular translocation of RhoA. Treatment with MβCD, 50 ng/ml C3 exoenzyme (a RhoA inhibitor) or 50 nM latrunculin B (actin filaments depolymerization agent) significantly attenuated leptin-induced RhoA translocation into caveolae fractions. Moreover, Western blot analysis showed that leptin-dependent activation of PI3K (116%; p<0.05), Akt (115%; p<0.05) and RhoA (330%; p<0.05) were significantly inhibited by 50 μM LY294002, a specific PI3K inhibitor. In addition, LY294002 significantly attenuated leptin-induced increases in cell surface area and in leucine incorporation. Furthermore, we found that leptin-induced activation of p38 (189%; p<0.05) and ERK1/2 (220%; p<0.05) was associated with p38 MAPK but not ERK1/2 nuclear translocation. MβCD, C3 exoenzyme and LY294002 potently attenuated leptin-induced p38 MAPK nuclear translocation. Conclusions : Our results demonstrate that caveolae, the PI3K/Akt/RhoA pathway and p38 MAPK nuclear translocation play a pivotal role in leptin-induced cardiomyocyte hypertrophy.

scholarly journals Mechanism of miR-218-5p in autophagy, apoptosis and oxidative stress in rheumatoid arthritis synovial fibroblasts is mediated by KLF9 and JAK/STAT3 pathways

2021 ◽  
pp. jim-2020-001437
Author(s):  
Ming Chen ◽  
Minghui Li ◽  
Na Zhang ◽  
Wenwen Sun ◽  
Hui Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Stress ◽  
Signaling Pathway ◽  
Synovial Tissue ◽  
Synovial Fibroblasts ◽  
Reverse Transcription Pcr ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Interfering Rna ◽  
And Oxidative Stress

This study was aimed to investigate the effects of miR-218-5p on the proliferation, apoptosis, autophagy, and oxidative stress of rheumatoid arthritis synovial fibroblasts (RASFs), and the related mechanisms. Quantitative reverse transcription–PCR showed that the expression of miR-218-5p in rheumatoid arthritis synovial tissue was significantly higher than that in healthy synovial tissue. Compared with healthy synovial fibroblasts, miR-218-5p expression was obviously upregulated in RASFs, while KLF9 protein expression was markedly downregulated. Mechanistically, miR-218-5p could directly bind to the 3′ untranslated region of KLF9 to inhibit the expression of KLF9. Additionally, transfection of miR-218-5p small interfering RNA (siRNA) inhibited the proliferation but promoted apoptosis and autophagy of RASFs. Simultaneously, miR-218-5p silencing reduced reactive oxygen species and malondialdehyde levels and increased superoxide dismutase and glutathione peroxidase activity to improve oxidative stress in RASFs. More importantly, the introduction of KLF9 siRNA reversed the effects of miR-218-5p siRNA transfection on RASF proliferation, apoptosis, autophagy, and oxidative stress. What is more, silencing miR-218-5p inhibited the activation of JAK2/STAT3 signaling pathway by targeting KLF9. Collectively, knockdown of miR-218-5p could regulate the proliferation, apoptosis, autophagy and oxidative stress of RASFs by increasing the expression of KLF9 and inhibiting the activation of the JAK2/STAT3 signaling pathway, which may provide a potential target for the mechanism research of RA.

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