PMID- 33383564 OWN - NLM STAT- MEDLINE DCOM- 20210422 LR - 20240226 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 537 DP - 2021 Jan 22 TI - Exogenous hydrogen sulfide inhibits neutrophils extracellular traps formation via the HMGB1/TLR4/p-38 MAPK/ROS axis in hyperhomocysteinemia rats. PG - 7-14 LID - S0006-291X(20)32236-1 [pii] LID - 10.1016/j.bbrc.2020.12.059 [doi] AB - Hydrogen sulfide (H(2)S) prevents platelet activation and neutrophils extracellular traps (NETs) formation. However, the mechanism of sodium hydrosulfide (NaHS, a donor that produces H(2)S) inhibits the formation of NETs in hyperhomocysteinemia (HHcy) rats has not been previously investigated. In the experiment, the expressions of HMGB1 of platelets, the expressions of TLR4, PAD4 and the phosphor-p38 of neutrophils were measured. The NETs formations, the concentration of DNA in the serum and the culture solution of cultured neutrophils which was stimulated by platelet-rich plasma (PRP) were tested. Additionally, the cellular ROS level and SOD activity were detected. The platelets were activated and the expression of HMGB1 of platelets and NETs formation, the concentration of DNA, and the expressions of TLR4, phosphor-p38 and PAD4, the ROS level were all increased while the activity of SOD decreased in the HHcy group compared to the control group. NaHS significantly inhibited the activation of platelets, the production of ROS and the formation of NETs in neutrophils, reversed the expressions of HMGB1, TLR4, phosphor-p38, PAD4 and decreased concentration of DNA which was caused by high homocysteine. Our results demonstrate that the donor of H(2)S inhibits NETs formation of neutrophils via the HMGB1/TLR4/p38 MAPK/ROS pathway in hyperhomocysteinemia. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Zhao, Xueying AU - Zhao X AD - Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China. FAU - Zhang, Liyuan AU - Zhang L AD - Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China. FAU - Liu, Xin AU - Liu X AD - Department of Pathophysiology, Harbin Medical University, Harbin, 150080, China. FAU - Zhao, Ziqing AU - Zhao Z AD - Department of Pathophysiology, Harbin Medical University, Harbin, 150080, China; Department of Pathology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, 361004, China. FAU - Zhong, Xin AU - Zhong X AD - Department of Pathophysiology, Harbin Medical University, Harbin, 150080, China. Electronic address: xzhong1111@hrbmu.edu.cn. FAU - Wang, Yuwen AU - Wang Y AD - Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China. Electronic address: yuww1111@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201228 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (HMGB1 Protein) RN - 0 (Reactive Oxygen Species) RN - 0 (Toll-Like Receptor 4) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 3.5.3.15 (Protein-Arginine Deiminase Type 4) RN - YY9FVM7NSN (Hydrogen Sulfide) SB - IM MH - Animals MH - Blood Platelets/drug effects/metabolism/ultrastructure MH - Disease Models, Animal MH - Extracellular Traps/drug effects/*metabolism MH - HMGB1 Protein/*metabolism MH - Hydrogen Sulfide/*pharmacology MH - Hyperhomocysteinemia/*metabolism MH - Male MH - Neutrophils/drug effects/metabolism MH - Phosphorylation/drug effects MH - Platelet-Rich Plasma/metabolism MH - Protein-Arginine Deiminase Type 4/metabolism MH - Rats, Wistar MH - Reactive Oxygen Species/*metabolism MH - Signal Transduction/drug effects MH - Toll-Like Receptor 4/*metabolism MH - p38 Mitogen-Activated Protein Kinases/*metabolism MH - Rats OTO - NOTNLM OT - Exogenous hydrogen sulfide OT - High-mobility group box 1 OT - Neutrophils extracellular traps OT - ROS OT - Toll-like receptor 4 COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2021/01/01 06:00 MHDA- 2021/04/23 06:00 CRDT- 2020/12/31 20:18 PHST- 2020/12/16 00:00 [received] PHST- 2020/12/17 00:00 [accepted] PHST- 2021/01/01 06:00 [pubmed] PHST- 2021/04/23 06:00 [medline] PHST- 2020/12/31 20:18 [entrez] AID - S0006-291X(20)32236-1 [pii] AID - 10.1016/j.bbrc.2020.12.059 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2021 Jan 22;537:7-14. doi: 10.1016/j.bbrc.2020.12.059. Epub 2020 Dec 28.