title: Ferulate protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in tert-butyl hydroperoxide-induced Caco-2 cells.
abstract: Epithelial barrier function is determined by both transcellular and paracellular permeability, the latter of which is mainly influenced by tight junctions (TJs) and apoptotic leaks within the epithelium. We investigated the protective effects of ferulate on epithelial barrier integrity by examining permeability, TJ protein expression, and apoptosis in Caco-2 cells treated with tert-butyl hydroperoxide (t-BHP), a strong reactive species inducer. Caco-2 cells pretreated with ferulate (5 or 15 μM) were exposed to t-BHP (100 μM), and ferulate suppressed the t-BHP-mediated increases in reactive species and epithelial permeability in Caco-2 cells. Moreover, ferulate inhibited epithelial cell leakage induced by t-BHP, which was accompanied by decreased expression of the TJ proteins zonula occludens-1 and occludin. In addition, pretreatment with ferulate markedly protected cells against t-BHP-induced apoptosis, as evidenced by decreased nuclear condensation, cytochrome c release, and caspase-3 cleavage and an increased Bax/Bcl-2 ratio. These results suggest that ferulate protects the epithelial barrier of Caco-2 cells against oxidative stress, which results in increased epithelial permeability, decreased TJ protein expression, and increased apoptosis. The most significant finding of our study is the demonstration of protective, ferulate-mediated antioxidant effects on barrier integrity, with a particular focus on intracellular molecular mechanisms.
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan, Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Eun Kyeong
authors.initials: EK
authors.lastname: Lee
authors.forename: Min Hi
authors.initials: MH
authors.lastname: Park
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Ha
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Jung
authors.forename: Min-Sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: Byung Pal
authors.initials: BP
authors.lastname: Yu
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells; D053148:Caspase 3 / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002470:Cell Survival; D003373:Coumaric Acids / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D062793:Occludin / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000009:adverse effects
chemical_list: D000975:Antioxidants; C494826:BAX protein, human; D003373:Coumaric Acids; C568985:OCLN protein, human; D062793:Occludin; D019253:Proto-Oncogene Proteins c-bcl-2; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D020122:tert-Butylhydroperoxide; C004999:ferulic acid; C505407:CASP3 protein, human; D053148:Caspase 3