Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China
Zongmin Li
State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences • Beijing, Beijing Institute of Lifeomics, Beijing, 102206, China; Anhui Medical University, Hefei, 230032, China
Lulu Zhang
Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China
Huan Tang
Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China
Heng Zhang
Department of Endocrinology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China
Chu Wang
Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China
Selena Ying Chen
Division of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093, USA
Dingfang Bu
Laboratory Center, Peking University First Hospital, Beijing, 100034, China
Zaifeng Zhang
Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China
Zhigang Zhu
Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China
Piaoliu Yuan
Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China
Kun Li
Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu, 610064, China
Xiaoqi Yu
Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu, 610064, China
Wei Kong
Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191, China; Key Laboratory of Cardiovascular Sciences, Ministry of Education, China
Chaoshu Tang
Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191, China; Key Laboratory of Cardiovascular Sciences, Ministry of Education, China
Youngeun Jung
Department of Chemistry, The Scripps Research Institute, Jupiter, FL, 33458, USA
Renan B. Ferreira
Department of Chemistry, The Scripps Research Institute, Jupiter, FL, 33458, USA
Kate S. Carroll
Department of Chemistry, The Scripps Research Institute, Jupiter, FL, 33458, USA
Junbao Du
Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China; Key Laboratory of Cardiovascular Sciences, Ministry of Education, China
Jing Yang
State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences • Beijing, Beijing Institute of Lifeomics, Beijing, 102206, China; Anhui Medical University, Hefei, 230032, China; Corresponding author. State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences • Beijing, Beijing Institute of Lifeomics, Beijing, 102206, China.
Hongfang Jin
Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China; Key Laboratory of Cardiovascular Sciences, Ministry of Education, China; Corresponding author. Department of Pediatrics, Peking University First Hospital, Beijing, 100034, Key Laboratory of Cardiovascular Sciences, Ministry of Education, China.
Sulfur dioxide (SO2) has emerged as a physiological relevant signaling molecule that plays a prominent role in regulating vascular functions. However, molecular mechanisms whereby SO2 influences its upper-stream targets have been elusive. Here we show that SO2 may mediate conversion of hydrogen peroxide (H2O2) to a more potent oxidant, peroxymonosulfite, providing a pathway for activation of H2O2 to convert the thiol group of protein cysteine residues to a sulfenic acid group, aka cysteine sulfenylation. By using site-centric chemoproteomics, we quantified >1000 sulfenylation events in vascular smooth muscle cells in response to exogenous SO2. Notably, ~42% of these sulfenylated cysteines are dynamically regulated by SO2, among which is cysteine-64 of Smad3 (Mothers against decapentaplegic homolog 3), a key transcriptional modulator of transforming growth factor β signaling. Sulfenylation of Smad3 at cysteine-64 inhibits its DNA binding activity, while mutation of this site attenuates the protective effects of SO2 on angiotensin II-induced vascular remodeling and hypertension. Taken together, our findings highlight the important role of SO2 in vascular pathophysiology through a redox-dependent mechanism.
