III. Intracellular signaling in response to toxic liver injury.
Toxin-induced liver injury was formerly considered a passive biochemical event, but recent evidence has demonstrated that signal transduction pathways actively modulate the hepatocyte's response to this form of injury. Investigations have examined the effects of a variety of toxins on the activation of receptor-coupled signal transduction, mitogen-activated protein kinases, and Fas signaling, as well as the generation of second messengers such as ceramide and nitric oxide. Many of these pathways culminate in the activation of transcription factors such as activator protein-1, c-Myc, or nuclear factor-kappaB. This Themes article discusses the effects of toxic injury on these signaling pathways and their known functions in regulating hepatocyte death and proliferation following injury.
Jones
B E
BE
Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Czaja
M J
MJ
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D053222:Fas Ligand Protein; D006801:Humans; D008099:Liver / Q000293:injuries / Q000473:pathology* / Q000503:physiopathology*; D008562:Membrane Glycoproteins / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013107:Sphingolipids / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D019014:fas Receptor / Q000502:physiology
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D013107:Sphingolipids; D014157:Transcription Factors; D019014:fas Receptor; D009569:Nitric Oxide; D017871:Calcium-Calmodulin-Dependent Protein Kinases