title: Characteristics of intracellular Ca2+signals consisting of two successive peaks in hepatocytes during liver regeneration after 70% partial hepatectomy in rats.
abstract: Two specific signals for regulating liver regeneration were found after 70% partial hepatectomy (PH) in rats. The first finding was a sustained increasing signal of intracellular Ca2+([Ca2+]i) in hepatocytes, consisting of two successive peaks with the first narrow peak at 1 hour and the second broad peak increasing by day 3 and then returning to normal by day 4. The second finding was an abnormal peak in the restoring ratio (Rr) curve of liver regeneration after 70% PH at day 4, where the Rrexceeded 100% temporarily, returned to a lower level, and then proceeded to a termination phase of liver regeneration. For 4 days around the two successive [Ca2+]ipeaks and abnormal peak, various physiological activities were induced to promote liver regeneration after 70% PH. mRNA expression of genes encoding Ca2+-binding proteins S100A4 and calpain was induced between the two Ca2+peaks. Hepatocytes underwent synchronous cell proliferation as the liver was restored from 30% to 70% at day 4, and significant expression ofVEGFmRNA at around day 4 promoted angiogenesis to remodel the sinusoidal system. Cytochrome P450 activity levels in microsomes and alanine aminotransferase values at 24 hours after CCl4administration were decreased after 70% PH, which recovered transiently to the control level at day 4, returned to the decreased level, and then slowly recovered by day 10. Thus, these results indicate that day 4 is important during liver regeneration after 70% PH.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
authors.forename: Zenei
authors.initials: Z
authors.lastname: Taira
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Monmasu
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamase
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Miyake
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
authors.forename: Maya
authors.initials: M
authors.lastname: Shiraishi
keywords: S100A4; intracellular Ca2+; partial hepatectomy; ratio of liver regeneration; termination signal