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Abstract：
UNASSIGNED: Endogenous sulfur dioxide (SO2) 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 SO2 suppressed myocardial fibrosis.
UNASSIGNED: 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 SO2 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 SO2 sulfenylated ERK1/2, and inhibited ERK1/2 phosphorylation and cardiac fibroblast proliferation, while a sulfhydryl reducing agent dithiothreitol (DTT) reversed the above effects of SO2. Furthermore, mutant ERK1C183S (cysteine 183 to serine) abolished the sulfenylation of ERK by SO2, thereby preventing the inhibitory effects of SO2 on ERK1 phosphorylation and cardiac fibroblast proliferation.
UNASSIGNED: Our study suggested that SO2 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 SO2 as a novel therapeutic target for myocardial fibrosis.
UNASSIGNED: 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 SO2 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 SO2 sulfenylated ERK1/2, and inhibited ERK1/2 phosphorylation and cardiac fibroblast proliferation, while a sulfhydryl reducing agent dithiothreitol (DTT) reversed the above effects of SO2. Furthermore, mutant ERK1C183S (cysteine 183 to serine) abolished the sulfenylation of ERK by SO2, thereby preventing the inhibitory effects of SO2 on ERK1 phosphorylation and cardiac fibroblast proliferation.
UNASSIGNED: Our study suggested that SO2 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 SO2 as a novel therapeutic target for myocardial fibrosis.
摘要：
■内源性二氧化硫（SO2）通过抑制心脏成纤维细胞的过度生长，在保护心脏免受心肌纤维化中起着至关重要的作用。本研究旨在探讨SO2抑制心肌纤维化的潜在机制。
■采用血管紧张素II(AngII)诱导的心脏纤维化的小鼠模型和AngII刺激的心脏成纤维细胞增殖的细胞模型。我们的发现发现，SO2减轻了AngII诱导的细胞外信号调节激酶1/2（ERK1/2）的异常磷酸化，导致成纤维细胞增殖的减少。机械上,第一次,我们发现SO2磺酰基化ERK1/2，并抑制ERK1/2磷酸化和心脏成纤维细胞增殖，而巯基还原剂二硫苏糖醇（DTT）逆转了SO2的上述作用。此外，突变型ERK1C183S（半胱氨酸183为丝氨酸）消除了SO2对ERK的磺酰化，从而阻止了SO2对ERK1磷酸化和心脏成纤维细胞增殖的抑制作用。
■我们的研究表明，SO2通过使ERK1/2磺酰化并随后抑制ERK1/2磷酸化来抑制心脏成纤维细胞增殖。这些新发现可能会增强对心肌纤维化机制的理解，并强调SO2作为心肌纤维化新的治疗靶点的潜力。
■采用血管紧张素II(AngII)诱导的心脏纤维化的小鼠模型和AngII刺激的心脏成纤维细胞增殖的细胞模型。我们的发现发现，SO2减轻了AngII诱导的细胞外信号调节激酶1/2（ERK1/2）的异常磷酸化，导致成纤维细胞增殖的减少。机械上,第一次,我们发现SO2磺酰基化ERK1/2，并抑制ERK1/2磷酸化和心脏成纤维细胞增殖，而巯基还原剂二硫苏糖醇（DTT）逆转了SO2的上述作用。此外，突变型ERK1C183S（半胱氨酸183为丝氨酸）消除了SO2对ERK的磺酰化，从而阻止了SO2对ERK1磷酸化和心脏成纤维细胞增殖的抑制作用。
■我们的研究表明，SO2通过使ERK1/2磺酰化并随后抑制ERK1/2磷酸化来抑制心脏成纤维细胞增殖。这些新发现可能会增强对心肌纤维化机制的理解，并强调SO2作为心肌纤维化新的治疗靶点的潜力。
