title: Clarifying the signal network of salvianolic acid B using proteomic assay and bioinformatic analysis.
abstract: Salvianolic acid B (SB) is a natural compound with protective effect against ischemia-reperfusion heart injury. However, the signal network of SB including both direct target proteins and downstream signal-related proteins has not been clarified. In the present study, epidermal growth factor receptor (EGFR) was predicted to be the most possible direct protein target of SB by INVDOCK, a ligand-protein inverse-docking algorithm. Possible signal-related proteins of SB in H9C2 cells, including both under normal condition and under ischemia-reperfusion injury, were searched using 2-DE analysis. Totally, 14 signal-related proteins were found. Finally, signal network from EGFR to the signal-related proteins was established using bioinformatic analysis. Interestingly, 9 of the 14 signal-related proteins could be included in a network together with EGFR through direct interaction or only one intermediate partner. The signal cascade from EGFR to heat shock protein 27 (HSP27) and mitofilin (IMMT, inner membrane mitochondrial protein) might be the most important cascade. The signal network was certified by measuring the binding affinity of SB to EGFR in vitro, the effect of SB on internalization and phosphorylation of EGFR, the effect of SB on viability and proliferation of H9C2 cells, and the expression of inner membrane mitochondrial protein in the presence of EGFR inhibitor AG 1478.
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. China.
authors.forename: Li-Xing
authors.initials: LX
authors.lastname: Feng
authors.forename: Chun-Jie
authors.initials: CJ
authors.lastname: Jing
authors.forename: Kai-Lin
authors.initials: KL
authors.lastname: Tang
authors.forename: Lin
authors.initials: L
authors.lastname: Tao
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Cao
authors.forename: Wan-Ying
authors.initials: WY
authors.lastname: Wu
authors.forename: Shu-Hong
authors.initials: SH
authors.lastname: Guan
authors.forename: Bao-Hong
authors.initials: BH
authors.lastname: Jiang
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.forename: De-An
authors.initials: DA
authors.lastname: Guo
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000032:analysis* / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D019295:Computational Biology; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000032:analysis / Q000378:metabolism; D009124:Muscle Proteins / Q000032:analysis / Q000378:metabolism; D011485:Protein Binding; D040901:Proteomics; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D053630:Depsides
chemical_list: D001572:Benzofurans; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D055551:HSP27 Heat-Shock Proteins; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; C532603:mitofilin protein, mouse; C076944:salvianolic acid B; D053630:Depsides