title: p38 Mitogen-activated protein kinase and c-Jun NH2-terminal protein kinase regulate the accumulation of a tight junction protein, ZO-1, in cell-cell contacts in HaCaT cells.
abstract: To investigate the involvement of stress-activated protein kinases, JNK and p38 MAPK, in the assembly of tight junctions in keratinocytes, we treated HaCaT cells with various combinations of SP600125 (an inhibitor of JNK), SB202190 (an inhibitor of p38 MAPK) and anisomycin (an activator of both JNK and p38 MAPK) and examined the localization of ZO-1, an undercoat constitutive protein of the tight junction. Short-term (8h) incubation with SP600125, SB202190 or anisomycin induced the accumulation of ZO-1 in the cell-cell contacts, with reduced ZO-1 staining in the cytoplasm, while only long-term (24h) incubation with SP600125 induced the accumulation of ZO-1. SP600125, SB202190 or SP600125 plus SB202190 treatment induced thin linear staining for ZO-1 in the cell-cell contacts. Anisomycin treatment induced thick and irregular linear staining for ZO-1, while anisomycin plus SP600125 treatment induced zipper-like staining for ZO-1. Anisomycin plus SB202190 treatment or anisomycin plus both SP600125 and SB202190 treatment for 8h failed to lead to the accumulation of ZO-1 in cell-cell contacts, but induced thin linear staining with several gaps 16 h after removal of these agents. These results suggest that the localization of ZO-1 in cell-cell contacts is differently regulated by activation and inhibition of JNK and/or p38 MAPK depending on the incubation period.
authors.affiliation: Department of Odontology, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Minakami
authors.affiliation: Department of Morphological Biology, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Kitagawa
authors.affiliation: Laboratory of Zoology, Graduate School of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iida
authors.affiliation: Department of Odontology, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Anan
authors.affiliation: Department of Morphological Biology, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan. Electronic address: tinaitj@college.fdcnet.ac.jp.
authors.forename: Tetsuichiro
authors.initials: T
authors.lastname: Inai
mesh_terms: D000841:Anisomycin / Q000008:administration & dosage; D000873:Anthracenes / Q000008:administration & dosage; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D011725:Pyridines / Q000008:administration & dosage; D062826:Zonula Occludens-1 Protein / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000873:Anthracenes; D007093:Imidazoles; D011725:Pyridines; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C432165:pyrazolanthrone; D000841:Anisomycin; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole
keywords: HaCaT cell; Mitogen-activated protein kinase (MAPK); Tight junction; ZO-1; c-Jun NH(2)-terminal protein kinase (JNK); p38 MAPK