[Ursodeoxycholic acid inhibits hepatocyte-like cell apoptosis by down-regulating the expressions of Bax and Caspase-3].
OBJECTIVE
To investigate the mechanism of ursodeoxycholic acid (UDCA) in hepatocyte apoptosis using differentiated hepatocytes derived from bone marrow mesenchymal cells.


METHODS
Rat bone marrow mesenchymal cell was induced into mature hepatocytes in vitro and then treated with PBS (Cont), deoxycholic acid (DCA), DCA plus UDCA (U + D) or UDCA alone (UDCA). Cell apoptosis was detected by Hoechst staining and Caspase-3 activity measurement. The mRNA expressions of p53 and Bax were measured by semi-quantitative RT-PCR and real-time RT-PCR. The Bax protein expression was detected by immunohistochemistry.


RESULTS
In comparison with Cont, DCA obviously induced hepatocyte apoptosis as measured by an increased cell count and a higher Caspase-3 activity (P < 0.05). These increments could be inhibited by addition of UDCA. The expressions of p53 and Bax in hepatocytes were up-regulated by DCA. These up-expressions could also be inhibited by UDCA. The DCA-induced increased count of Bax-positive cells could be reduced by UDCA.


CONCLUSIONS
UDCA inhibits DCA-induced hepatocyte apoptosis by down-regulating the expression of p53/Bax signal molecule.
Department of General Surgery, Peking Union Medical Collage Hospital, Beijing, China.
Wen-juan
WJ
Ji
Qiang
Q
Qu
Ye
Y
Jin
Lei
L
Zhao
Xiao-dong
XD
He
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001854:Bone Marrow Cells; D053148:Caspase 3 / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
C494828:Bax protein, rat; D051028:bcl-2-Associated X Protein; D014580:Ursodeoxycholic Acid; C505410:Casp3 protein, rat; D053148:Caspase 3