Propofol protects hepatic L02 cells from hydrogen peroxide-induced apoptosis via activation of extracellular signal-regulated kinases pathway.
BACKGROUND
Propofol protects cells against ischemia/reperfusion injury in several organs, but there are few reports of its effect on liver epithelial cells. We investigated the effect of propofol preconditioning on human hepatic L02 cells under hydrogen peroxide (H2O2)-induced oxidative stress and attempted to determine whether the extracellular signal-regulated kinases (ERK) pathway is involved in this process.


METHODS
Preconditioned or nonpreconditioned human hepatic L02 cells were exposed to H2O2 and the changes of apoptosis were evaluated by TUNEL assay, Caspase-3 and poly ADP-ribose polymerase (PARP) cleavage. Activation of ERK1/2 and mitogen-activated protein kinase//ERK Kinase 1/2 (MEK1/2) was measured by Western blot analysis. The mRNA expression of Bcl-2, Bcl-x(L), Bad, and Bax was quantified by real-time quantitative reverse transcriptase polymerase chain reaction.


RESULTS
Propofol preconditioning reduced the population of apoptotic cells and Caspase-3 and PARP cleavage induced by H2O2 inhepatic L02 cells. L02 cells treated with propofol (0.01-0.3 mM) alone, led to a dose-dependent activation of ERK and MEK, and such activation was detected within 0.5 h and eventually declined to <50% at 4 h. The addition of the specific inhibitor PD98059 completely abolished the activation of ERK and aggravated the extent of apoptosis. Moreover, propofol treatment repressed the mRNA expression of proapoptotic genes Bad and Bax, and this repression could be partly reversed by PD98059.


CONCLUSIONS
These findings demonstrate that propofol protects hepatic L02 cells from H2O2-induced apoptosis, partly through activating the MEK-ERK pathway and further suppressing Bad and Bax expression.
Wang
Hao
H
Department of Anesthesiology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, People's Republic of China.
Xue
Zhanggang
Z
Wang
Qiong
Q
Feng
Xiaochen
X
Shen
Zonghou
Z
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000187:drug effects / Q000378:metabolism
D018686:Anesthetics, Intravenous; D003470:Culture Media; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D006861:Hydrogen Peroxide; D011065:Poly(ADP-ribose) Polymerases; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; D015742:Propofol