Sulforaphane modulates CX3CL1/CX3CR1 axis and inflammation in palmitic acid-induced cell injury in C2C12 skeletal muscle cells.

Abstract

Studies have shown that sulforaphane (SFN) has potent anti-inflammatory and free radical scavenging effects on obesity and associated disorder such as diabetes, polycystic ovary syndrome, and metabolic syndrome. fractalkine (CX3CL1) and its receptor, CX3CR1, play an important role in muscle metabolism by improving insulin-sensitizing effects. Here, in this study we examined the SFN effect on CX3CL1 and its receptor, CX3CR1, in C2C12 myotubes in palmitic acid (PA)-induced oxidative stress and inflammation. The results showed that PA (750 μM) evoked lipotoxicity as a reduction in cell viability, increased IL-6 and TNF-α expression, and enhanced reactive oxygen species (ROS). However, SFN pretreatment attenuated the levels of, IL-6 and TNF-α in C2C12 myotubes exposure to PA. Moreover, SFN pretreatment up-regulated nuclear factor erythroid related factor 2 (Nrf2) /heme oxygenase-1(HO-1) pathway protein in C2C12 cells as indicated by a decrease in ROS levels. Interestingly, PA also caused an increase in CX3CL1 and CX3CR1 expression that SFN abrogated it. We also found the protective effect of SFN agonist PA-induced lipotoxicity with promotes in UCP3 gene expression in C2C12 cells. Collectively, these findings suggest that SFN hampers the PA-induced inflammation in C2C12 cells by modulation of the Nrf2/HO-1 pathway and CX3CL1/CX3CR1 axis and may propose a new therapeutic approach to protect against obesity-associated disorders in skeletal muscle cells.

• Authors: Yousef Faridvand, Parinaz Haddadi, Hamid Reza Nejabati, Samad Ghaffari, Elham Zamani-Gharehchamani, Samira Nozari, Mohammad Nouri, Ahmadreza Jodati
• Journal: Molecular biology reports (Mol Biol Rep) Vol. 47 Issue 10 Pg. 7971-7977 (Oct 2020) ISSN: 1573-4978 [Electronic] Netherlands
• PMID: 33034881 (Publication Type: Journal Article)

Chemical References

• CX3C Chemokine Receptor 1
• Chemokine CX3CL1
• Cx3cl1 protein, mouse
• Cx3cr1 protein, mouse
• Interleukin-6
• Isothiocyanates
• Sulfoxides
• Tumor Necrosis Factor-alpha
• interleukin-6, mouse
• Palmitic Acid
• sulforaphane

Topics

• Animals
• CX3C Chemokine Receptor 1 (metabolism)
• Cell Line
• Chemokine CX3CL1 (metabolism)
• Interleukin-6 (metabolism)
• Isothiocyanates (pharmacology)
• Mice
• Myoblasts, Skeletal (metabolism, pathology)
• Palmitic Acid (toxicity)
• Sulfoxides (pharmacology)
• Tumor Necrosis Factor-alpha (metabolism)