title: Synchronized necrotic death of attached hepatocytes mediated via gap junctions.
abstract: Extensive studies have unveiled the intracellular molecular signaling pathways of cell death. To better understand cell death in tissues, it is important to investigate the influence of neighboring cells on the response to death stimuli. By time-lapse microscopy, we found that cells in couplets (two hepatocytes attached to each other) died independently when stimulated with anti-Fas antibody and staurosporine, whereas acetaminophen (APAP) and aryl alcohol caused synchronized cell death although its timing varied among different couplets. Synchronized death of couplets was not caused by APAP when hepatocytes were deficient in both Connexin26 and Connexin32, indicating a crucial role of gap junctions in the synchronized death process. We also demonstrated that APAP-sensitive male hepatocytes were protected by attachment to APAP-insensitive female hepatocytes, with this protection being dependent on gap junctions. These findings indicate that APAP-induced and aryl alcohol-induced necrotic death of hepatocytes is modulated by attached neighboring cells via gap junctions.
authors.affiliation: 1] Japan Society for the Promotion of Science (JSPS), Japan [2] Department of Medical Genetics, Osaka University Medical School, Osaka, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Saito
authors.affiliation: Department of Medical Genetics, Osaka University Medical School, Osaka, Japan.
authors.forename: Koei
authors.initials: K
authors.lastname: Shinzawa
authors.affiliation: Department of Medical Genetics, Osaka University Medical School, Osaka, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Tsujimoto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D000072259:Connexin 26; D017630:Connexins / Q000378:metabolism*; D005260:Female; D017629:Gap Junctions / Q000502:physiology*; D022781:Hepatocytes / Q000473:pathology* / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis / Q000473:pathology / Q000503:physiopathology; D012727:Sex Characteristics; D000097002:Gap Junction beta-1 Protein
chemical_list: D000072259:Connexin 26; D017630:Connexins; D000097002:Gap Junction beta-1 Protein