Farnesyl pyrophosphate synthase (FPPS) is a key enzyme in the mevalonate pathway. Our previous studies have indicated that cardiac-specific overexpression of FPPS induces cardiac hypertrophy and dysfunction in mice, and inhibition of FPPS prevents angiotensin (Ang) II-induced hypertrophy in cardiomyocytes. However, the role for FPPS in myocardial ischemia/reperfusion (MIR) injury is still not clear. The objective of this work was to investigate the effect of FPPS on MIR injury in H9c2 cells which were subjected to hypoxia/reoxygenation (HR) to mimic MIR. Prior to HR, cells were transfected with pE-mFPPS, shFPPS, or pE-GFP. Our results showed that the overexpression of FPPS reduced cell proliferation, increased cell injury and cell apoptosis, and knock-down of FPPS improved cell proliferation, decreased cell injury, and cell apoptosis after HR. Besides, overexpression of FPPS increased Rac1 activity and reactive oxygen species (ROS) generation, while FPPS silencing decreased Rac1 activity and ROS generation. Based on these findings, we propose that knock-down of FPPS reduces Rac1 activity and ROS production, and finally leads to the decrease of HR-induced injury in H9c2 cells. These findings point that FPPS might be a potential target in preventing H9c2 cells from HR-induced injury.
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http://dx.doi.org/10.1002/cbin.10795 | DOI Listing |
Sci Rep
January 2025
Department of Physiology, Zunyi Medical University, Campus No.1 Road, Xinpu New District, Zunyi, 563006, Guizhou, China.
In the vascular system, angiotensin II (Ang II) mediated vasoconstriction by inducing the production of 20-hydroxyeicosatetraenoic acid (20-HETE). However, the role of 20-HETE in Ang II-induced cardiac dysfunction had yet to be fully elucidated. This study investigated the effects of Ang II on CYP4A expression and 20-HETE production in H9c2 cells using RT-qPCR, Western blot, and ELISA.
View Article and Find Full Text PDFOpen Life Sci
December 2024
Department of Cardiology, The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, 563000, Guizhou, People's Republic of China.
We investigated the protective effect of the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC) on cardiomyocyte injury induced by HCN1 channel overexpression, and explored the underlying mechanisms. An HCN1 overexpression vector was constructed and transfected into H9C2 cells, followed by PDTC treatment. The experiments comprised the following groups: control, control + PDTC, overexpression negative control, HCN1 overexpression (HCN1-OE), and combined HCN1-OE + PDTC groups.
View Article and Find Full Text PDFCell Biochem Biophys
January 2025
Department of Pharmacy, The Fourth Affiliated Hospital of Soochow University, Jiangsu, Suzhou, 215000, China.
Total glucosides of paeony (TGP) have been investigated for their effects on cardiomyocyte hypertrophy induced by angiotensin II (Ang II). In this study, rat cardiomyocyte H9c2 cells were treated with various doses of TGP (0, 12.5, 25, 50, 100, 200, and 400 μmol/L), and cell viability was assessed using the MTT method to determine an optimal dose.
View Article and Find Full Text PDFInt J Mol Med
March 2025
Department of Clinical Laboratory, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing 400014, P.R. China.
Sepsis is often a cause of mortality in patients admitted to the intensive care unit. Notably, the heart is the organ most susceptible to the impact of sepsis and this condition is referred to as sepsis‑induced cardiomyopathy (SIC). Low triiodothyronine (T3) syndrome frequently occurs in patients with sepsis, and the heart is one of the most important target organs for the action of T3.
View Article and Find Full Text PDFDalton Trans
January 2025
Department of Applied Chemistry, Cochin University of Science and Technology, Kochi 22, Kerala, India.
The rise of various diseases demands the development of new agents with antioxidant, antimicrobial, anti-inflammatory, enzyme-inhibiting, and cytotoxic properties. In this study, heterocyclic Schiff base complexes of Cu(II) featuring a benzo[]thiophene moiety were synthesized and their biological activities evaluated. The complexes were characterized using FT-IR, UV-Vis, and EPR spectroscopy, TG-DTG analysis, magnetic moment measurements, molar conductivity measurements, and elemental analyses.
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