title: Alteration in the apoptosis process of rat esophageal epithelium with hyperproliferation of indigenous bacteria under a physiological condition.
abstract: The apoptosis process in rat esophageal epithelium was investigated using enzyme-immunohistochemistry and transmission electron microscopy. As a result, Fas and Fas-L were expressed in the epithelial cell membrane and cytoplasm from the stratum spinosum (SS) to the stratum granulosum (SG). No TNF-R1 show immunopositivity in the cell membranes. TNF-α and caspase-8 were not observed in any layer. Caspase-10, cleaved caspase-3, XIAP and DNase-1 were found in the epithelial cytoplasm from the SS to the SG, whereas Bid, Apaf-1 and cleaved caspase-9 were detected only in the SG. Cytochrome c was observed as cytoplasmic granular positivity from the stratum basale (SB) and altered into homogeneous immunopositivity in the SG. Bcl-2 and Bcl-X immunopositivity was detected in cytoplasm from the SB to the SG. Immunoreactions of Bak in the cytoplasm and Bax beneath the cell membrane were observed from the upper portion of the SS with increasing intensity toward the SG. In the sites with the hyperproliferation of indigenous bacteria, TNF-R1, TNF-α and caspase-8 were detected in the SG and the immunopositive intensities of Bid, Apaf-1 and cleaved caspase-9 were altered to be strong. Prominently swollen cells and decreased mitochondria were ultrastructurally confirmed in the uppermost layers of stratum corneum. These findings suggest that the Fas-Fas-L-interaction initially induces apoptosis through a mitochondria-independent pathway and secondarily through a mitochondria-dependent pathway, leading to eventual epithelial cell death in the rat esophageal epithelium. The bacterial stimuli probably enhance the mitochondria-dependent pathway through the TNF-R1-TNF-α interaction.
authors.affiliation: Laboratory of Histophysiology, Department of Bioresource Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657-8501, Japan.
authors.forename: Kankanam Gamage Sanath
authors.initials: KG
authors.lastname: Udayanga
authors.forename: Kyoji
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hidenori
authors.initials: H
authors.lastname: Miyata
authors.forename: Yuh
authors.initials: Y
authors.lastname: Yokoo
authors.forename: Youhei
authors.initials: Y
authors.lastname: Mantani
authors.forename: Ei-Ichrou
authors.initials: EI
authors.lastname: Takahara
authors.forename: Junichi
authors.initials: J
authors.lastname: Kawano
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hoshi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitagawa
mesh_terms: D000818:Animals; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics / Q000378:metabolism; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics / Q000378:metabolism; D001419:Bacteria / Q000254:growth & development*; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000382:microbiology / Q000502:physiology; D004848:Epithelium / Q000382:microbiology*; D004947:Esophagus / Q000382:microbiology*; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: C506594:Apaf1 protein, rat; D053477:Apoptotic Protease-Activating Factor 1; D051023:BH3 Interacting Domain Death Agonist Protein; C494774:Bak1 protein, rat; C494828:Bax protein, rat; C494816:Bid protein, rat; D053222:Fas Ligand Protein; C491898:Fas protein, rat; C505662:Faslg protein, rat; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D051636:X-Linked Inhibitor of Apoptosis Protein; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D045304:Cytochromes c; D053453:Caspase 9