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GYY4137, a hydrogen sulfide-releasing molecule, inhibits the inflammatory response by suppressing the activation of nuclear factor-kappa B and mitogen-activated protein kinases in Coxsackie virus B3-infected rat cardiomyocytes
- Source :
- Molecular Medicine Reports. 11:1837-1844
- Publication Year :
- 2014
- Publisher :
- Spandidos Publications, 2014.
-
Abstract
- GYY4137 is a water‑soluble, small molecule hydrogen sulfide (H2S)‑release agent that possesses potent cardioprotective and anti‑inflammatory properties in experimental models. Coxsackie virus B3 (CVB3) infection commonly causes viral myocarditis, which mainly involves immune cell infiltration, eventually resulting in heart failure. In the present study, the effects and underlying mechanisms of GYY4137 treatment of CVB3‑induced myocarditis were investigated. The effects of GYY4137 on CVB3‑induced nuclear factor‑kappa B (NF‑κB) activity were examined by western blotting, immunofluorescence and electrophoretic mobility shift assay. Mitogen‑activated protein kinase (MAPK) signaling protein expression levels were detected by western blotting. Cardiomyocyte damage‑related enzyme activities, such as lactate dehydrogenase (LDH) and creatine kinase MB (CK‑MB), were measured by ELISA, as well as the production of proinflammatory cytokines. The results revealed that GYY4137 suppressed CVB3‑induced secretion of LDH, CK‑MB and pro‑inflammatory cytokines, such as tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6. Furthermore, the activation of NF‑κB and the IκBα degradation induced by CVB3 were also inhibited by GYY4137. Notably, the phosphorylation of p38, ERK1/2 and JNK1/2 induced by CVB3 was also inhibited by GYY4137. In conclusion, the data demonstrate that GYY4137 exerts anti‑inflammatory effects in CVB3‑infected cardiomyocytes. This anti‑inflammatory mechanism may be associated with suppression of NF‑κB and MAPK signaling pathway activation.
- Subjects :
- MAPK/ERK pathway
Cancer Research
Morpholines
p38 mitogen-activated protein kinases
Active Transport, Cell Nucleus
Anti-Inflammatory Agents
Coxsackievirus Infections
Biology
Biochemistry
Proinflammatory cytokine
Genetics
Animals
Humans
Myocytes, Cardiac
Hydrogen Sulfide
Protein kinase A
Molecular Biology
Cells, Cultured
Kinase
NF-kappa B
Organothiophosphorus Compounds
Molecular biology
Enterovirus B, Human
Rats
Cell biology
DNA-Binding Proteins
Enzyme Activation
Myocarditis
Protein Transport
IκBα
Oncology
Proteolysis
Molecular Medicine
Phosphorylation
Tumor necrosis factor alpha
Inflammation Mediators
Mitogen-Activated Protein Kinases
Subjects
Details
- ISSN :
- 17913004 and 17912997
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Molecular Medicine Reports
- Accession number :
- edsair.doi.dedup.....9c94994e7f6fb5330160a57ff4eab00a