title: Polyphenols differentially inhibit degranulation of distinct subsets of vesicles in mast cells by specific interaction with granule-type-dependent SNARE complexes.
abstract: Anti-allergic effects of dietary polyphenols were extensively studied in numerous allergic disease models, but the molecular mechanisms of anti-allergic effects by polyphenols remain poorly understood. In the present study, we show that the release of granular cargo molecules, contained in distinct subsets of granules of mast cells, is specifically mediated by two sets of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, and that various polyphenols differentially inhibit the formation of those SNARE complexes. Expression analysis of RBL-2H3 cells for 11 SNARE genes and a lipid mixing assay of 24 possible combinations of reconstituted SNAREs indicated that the only two active SNARE complexes involved in mast cell degranulation are Syn (syntaxin) 4/SNAP (23 kDa synaptosome-associated protein)-23/VAMP (vesicle-associated membrane protein) 2 and Syn4/SNAP-23/VAMP8. Various polyphenols selectively or commonly interfered with ternary complex formation of these two SNARE complexes, thereby stopping membrane fusion between granules and plasma membrane. This led to the differential effect of polyphenols on degranulation of three distinct subsets of granules. These results suggest the possibility that formation of a variety of SNARE complexes in numerous cell types is controlled by polyphenols which, in turn, might regulate corresponding membrane trafficking.
authors.affiliation: Department of Genetic Engineering, College of Biotechnology and Bioengineering, and Center for Human Interface Nano Technology, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, South Korea.
authors.forename: Yoosoo
authors.initials: Y
authors.lastname: Yang
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Oh
authors.forename: Paul
authors.initials: P
authors.lastname: Heo
authors.forename: Jae Yoon
authors.initials: JY
authors.lastname: Shin
authors.forename: Byoungjae
authors.initials: B
authors.lastname: Kong
authors.forename: Jonghyeok
authors.initials: J
authors.lastname: Shin
authors.forename: Ji-Chun
authors.initials: JC
authors.lastname: Lee
authors.forename: Jeong Su
authors.initials: JS
authors.lastname: Oh
authors.forename: Kye Won
authors.initials: KW
authors.lastname: Park
authors.forename: Choong Hwan
authors.initials: CH
authors.lastname: Lee
authors.forename: Yeon-Kyun
authors.initials: YK
authors.lastname: Shin
authors.forename: Dae-Hyuk
authors.initials: DH
authors.lastname: Kweon
mesh_terms: D015550:Cell Degranulation / Q000187:drug effects*; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006632:Histamine / Q000378:metabolism; D006801:Humans; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D046912:Multiprotein Complexes / Q000378:metabolism; D059808:Polyphenols / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D050600:SNARE Proteins / Q000378:metabolism*; D013379:Substrate Specificity / Q000187:drug effects; D022161:Transport Vesicles / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D059808:Polyphenols; D050600:SNARE Proteins; D006632:Histamine; D001619:beta-N-Acetylhexosaminidases