Effect of bilirubin on lipid peroxidation, sphingomyelinase activity, and apoptosis induced by sphingosine and UV irradiation.
The effect of bilirubin (BR) on sphingomyelin cycle activity, lipid peroxidation (LPO), and apoptosis induced by sphingosine and UV irradiation has been studied in vivo. Neutral Mg(2+)-dependent sphingomyelinase (SMase) activity and LPO level were monitored in heart, kidney, and liver of mice after administration of BR. BR inhibited both LPO and SMase activities in heart and kidney. BR induced a mild increase in LPO level and moderate increase in lipid contents in liver, consistent with the functional role of liver in both BR and lipid metabolism. BR injected to mice causes simultaneous and unidirectional alterations in both LPO level and SMase activity with a significant (p < 0.05) positive linear correlation between these two parameters. Sphingosine administration results in increased lipid peroxidation in murine liver. Data on DNA fragmentation indicate that exogenous BR may effectively protect thymus cells against sphingosine- and UV-mediated apoptosis. These results have revealed a biochemical association between oxidative stress and BR on one hand and the sphingomyelin cycle and apoptotic cell death on the other hand. Our data show that BR as an antioxidant, due to its effect on the sphingomyelin cycle, can protect membrane lipids against peroxidation and cells against apoptosis induced by various factors.
Dudnik
L B
LB
Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, ul. Kosygina 4, Moscow, 117977 Russia. lbd@sky.chph.ras.ru
Tsyupko
A N
AN
Khrenov
A V
AV
Alessenko
A V
AV
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D001663:Bilirubin / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000528:radiation effects; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D013108:Sphingomyelin Phosphodiesterase / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D013110:Sphingosine / Q000494:pharmacology*; D014466:Ultraviolet Rays
D013108:Sphingomyelin Phosphodiesterase; D013110:Sphingosine; D001663:Bilirubin