[Relationship of tumor necrosis factor alpha expression with activation of sphingomyelinase and lipid peroxidation after removal of cholestatic factor].
The goal of this work was to study the expression of tumor necrosis factor alpha (TNFalpha), sphingomyelin cycle activation, and lipid peroxidation (LPO) processes after the removal of a cholestatic factor in the liver subjected to different durations of cholestasis. Restored bile flow after a 9-day hepatic cholestasis normalized sphingomyelinase (SMase) activity and levels of TNFalpha and LPO products. The removal of a cholestatic factor after a 12-day cholestasis did not normalize the studied parameters: SMase activity and the levels of TNFalpha and LPO products remained much higher compared to control. A significant positive correlation between TNFalpha expression, SMase activity, and LPO rate has been revealed. The obtained data indicate that hepatocyte apoptosis after bile outflow restoration in late cholestasis can be due to the activation of the sphingomyelin cycle, LPO, and TNFalpha expression. The synergistic interaction can sharply increase the proapoptotic capacity of each of these factors since TNFalpha activates SMase and LPO, SMase activity depends on the LPO rate, while ceramide, an SMase-produced secondary messenger of apoptosis, can induce oxidative stress.
Dudnik
L B
LB
Tsiupko
A N
AN
Shupik
M A
MA
Akhaladze
G G
GG
Gal'perin
E I
EI
Platonova
L V
LV
Pantaz
E A
EA
Iasnetsov
V V
VV
Smirnov
L D
LD
Alesenko
A V
AV
D000818:Animals; D017209:Apoptosis; D001651:Cholestasis, Extrahepatic / Q000378:metabolism*; D015227:Lipid Peroxidation; D008099:Liver / Q000737:chemistry; D051381:Rats; D013108:Sphingomyelin Phosphodiesterase / Q000032:analysis / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D013108:Sphingomyelin Phosphodiesterase