Sulfenylation of ERK1/2: A novel mechanism for SO-mediated inhibition of cardiac fibroblast proliferation.

BACKGROUND

Endogenous sulfur dioxide (SO) plays a crucial role in protecting heart from myocardial fibrosis by inhibiting the excessive growth of cardiac fibroblasts. This study aimed to investigate potential mechanisms by which SO suppressed myocardial fibrosis.

METHODS AND RESULTS

Mouse model of angiotensin II (Ang II)-induced cardiac fibrosis and cell model of Ang II-stimulated cardiac fibroblast proliferation were employed. Our findings discovered that SO mitigated the aberrant phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) induced by Ang II, leading to a reduction of fibroblast proliferation. Mechanistically, for the first time, we found that SO sulfenylated ERK1/2, and inhibited ERK1/2 phosphorylation and cardiac fibroblast proliferation, while a sulfhydryl reducing agent dithiothreitol (DTT) reversed the above effects of SO. Furthermore, mutant ERK1 (cysteine 183 to serine) abolished the sulfenylation of ERK by SO, thereby preventing the inhibitory effects of SO on ERK1 phosphorylation and cardiac fibroblast proliferation.

CONCLUSION

Our study suggested that SO inhibited cardiac fibroblast proliferation by sulfenylating ERK1/2 and subsequently suppressing ERK1/2 phosphorylation. These new findings might enhance the understanding of the mechanisms underlying myocardial fibrosis and emphasize the potential of SO as a novel therapeutic target for myocardial fibrosis.