Cell death in pancreatitis: effects of alcohol.
Pancreatitis is a severe and frequently lethal disorder, a major cause of which is alcohol abuse. Parenchymal cell death is a major complication of pancreatitis. In experimental models of (non-alcoholic) acute pancreatitis, acinar cells have been shown to die through both necrosis and apoptosis, the two principal pathways of cell death. The severity of experimental acute pancreatitis correlates directly with the extent of necrosis and inversely with apoptosis. Thus, understanding the regulation of apoptosis and necrosis, and whether it is possible to manipulate the pattern of death responses, is becoming exceedingly important in investigations of the pathogenesis and treatment of pancreatitis. The effects of alcohol on cell death responses of pancreatitis, and the mechanisms that may mediate these effects, are just starting to be explored. This paper reviews the signaling pathways mediating the balance between apoptosis and necrosis in acute pancreatitis, and alcohol's effects on cell death responses in pancreatitis.
Gukovskaya
Anna S
AS
Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California 90073, USA. agukovsk@ucla.edu
Mareninova
Olga A
OA
Odinokova
Irina V
IV
Sung
Kai-Feng
KF
Lugea
Aurelia
A
Fischer
Lars
L
Wang
Yan-Ling
YL
Gukovsky
Ilya
I
Pandol
Stephen J
SJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D000431:Ethanol / Q000633:toxicity*; D009336:Necrosis / Q000139:chemically induced*; D019512:Pancreatitis, Alcoholic / Q000473:pathology*; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction
D000431:Ethanol; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506251:Ripk1 protein, mouse; D020169:Caspases