title: MAPKs and Hsc70 are critical to the protective effect of molecular hydrogen during the early phase of acute pancreatitis.
abstract: Molecular hydrogen (H2 ) has been proven to be an effective agent that can cure multiple organ diseases by reducing oxidative stress. Although the protective effect of hydrogen on acute pancreatitis (AP) has been confirmed, its molecular mechanism is still unclear. In this article, we aimed to investigate the changes in pancreatic cell protein expression associated with the protective effect of H2 against AP and attempted to uncover the molecular mechanism underlying this process. A proteomic analysis identified 73 differentially expressed proteins and generated the protein-protein interaction networks of these proteins. The results triggered our interest in mitogen-activated protein kinase (MAPK) and heat shock cognate 71 kDa protein (Hsc70). The subsequent in vitro experiments showed that H2 treatment inhibited the phosphorylation of extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 MAPK, and activated NF-κB and the expression of tumor necrosis factor α and interleukin-1β, while simultaneously preventing the translocation of phospho-ERK, phospho-JNK, and phospho-p38 from the cytoplasm to the nucleus. Furthermore, Hsc70 expression was upregulated by H2 administration. The animal experimental results were consistent with those of the in vitro experiments. In conclusion, H2 treatment can ameliorate the inflammatory response and reduce the expression of inflammatory mediators during the early phase of AP by inhibiting the MAPK pathways and increasing Hsc70 expression.
authors.affiliation: Department of Hepatobiliary Surgery, Yantai Yuhuangding Hospital of Qingdao University Medical College, China.|Department of Pancreatic and Biliary Surgery, First Affiliated Hospital of Harbin Medical University, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Emergency Surgery, First Affiliated Hospital of Harbin Medical University, China.
authors.forename: Haoxin
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Pancreatic and Biliary Surgery, First Affiliated Hospital of Harbin Medical University, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Jia
authors.affiliation: Department of Pancreatic and Biliary Surgery, First Affiliated Hospital of Harbin Medical University, China.
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pancreatic and Biliary Surgery, First Affiliated Hospital of Harbin Medical University, China.
authors.forename: Zengfu
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Pancreatic and Biliary Surgery, First Affiliated Hospital of Harbin Medical University, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Central Laboratory, First Affiliated Hospital of Harbin Medical University, China.
authors.forename: Shangha
authors.initials: S
authors.lastname: Pan
authors.affiliation: Department of Pancreatic and Biliary Surgery, First Affiliated Hospital of Harbin Medical University, China.
authors.forename: Xuewei
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Pancreatic and Biliary Surgery, First Affiliated Hospital of Harbin Medical University, China.
authors.forename: Jiachen
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Pancreatic and Biliary Surgery, First Affiliated Hospital of Harbin Medical University, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Sun
mesh_terms: D000208:Acute Disease; D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D050883:HSC70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006859:Hydrogen / Q000494:pharmacology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D010195:Pancreatitis / Q000201:enzymology / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D050883:HSC70 Heat-Shock Proteins; D012333:RNA, Messenger; D006859:Hydrogen; D020928:Mitogen-Activated Protein Kinases
keywords: Hsc70; MAPK pathway; acute pancreatitis; molecular hydrogen; proteomics