Buchumschlag

Ethanol-induced apoptosis in hepatoma cells proceeds via intracellular Ca2+ elevation, activation of TLCK-sensitive proteases, and cytochrome c release

Ethanol is known to induce apoptosis in hepatocytes. However, intracellular signaling events of ethanol-induced death are still only partially understood. We studied such processes in ethanol-induced apoptosis in HepG2 cells as a model system for human liver cells. We determined the incidence of apo...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Nakayama, Nobuaki (VerfasserIn) , Müller-Schilling, Martina (VerfasserIn) , Krammer, Peter H. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2001
In: Experimental cell research
Year: 2001, Jahrgang: 269, Heft: 2, Pages: 202-213
ISSN:1090-2422
DOI:10.1006/excr.2001.5319
Online-Zugang:Verlag, Volltext: https://doi.org/10.1006/excr.2001.5319
Verlag, Volltext: https://www.sciencedirect.com/science/article/pii/S0014482701953194
Volltext
Verfasserangaben:Nobuaki Nakayama, Sören T. Eichhorst, Martina Müller, Peter H. Krammer
Beschreibung
Zusammenfassung:Ethanol is known to induce apoptosis in hepatocytes. However, intracellular signaling events of ethanol-induced death are still only partially understood. We studied such processes in ethanol-induced apoptosis in HepG2 cells as a model system for human liver cells. We determined the incidence of apoptosis by DNA fragmentation and tested the effects of various known inhibitors. Ethanol induces apoptosis in HepG2 cells in a dose- and time-dependent manner as well as in rat primary hepatocytes. This effect was not mediated through the death receptor CD95 and the tumor necrosis factor receptors. It was efficiently inhibited by the caspase inhibitor N-benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone (zVAD-fmk), the Ca2+ chelator EGTA, and the serine protease inhibitor N-p-tosyl-l-lysine chloromethyl ketone (TLCK). Upon ethanol treatment, the intracellular calcium ion concentration was increased and cytochrome c was released from the mitochondria, and caspases were activated. EGTA and TLCK could inhibit cytochrome c release from the mitochondria. Furthermore, overexpression of Bcl-xL saved cells from ethanol-induced apoptosis. These data suggest that ethanol-induced apoptosis in liver cells is initiated by the intracellular Ca2+ elevation in the cytoplasm and activation of TLCK-sensitive serine proteases. Our data provide new insight into ethanol-induced apoptosis in liver cells and may lead to therapeutic strategies to prevent liver damage.
Beschreibung:Available online 25 May 2002
Elektronische Reproduktion der Druck-Ausgabe
Gesehen am 20.04.2021
Beschreibung:Online Resource
ISSN:1090-2422
DOI:10.1006/excr.2001.5319

Ähnliche Einträge