Submitted on June 22, 2005
Accepted on January 30, 2006
Differential regulation of the JNK/AP-1 pathway by S-Adenosylmethionine and methylthioadenosine in primary rat hepatocytes versus HuH7 hepatoma cells
Eduardo Ansorena1, Carmen Berasain2, Maria J. Lopez Zabalza1, Matias A. Avila2, Elena R. Garcia-Trevijano2, and Maria J. Iraburu1*
1 Departamento de Bioquimica y Biologia Molecular, Universidad de Navarra, Pamplona, Navarra, Spain
2 Area de Hepatologia y Terapia Genica, CIMA, Universidad de Navarra, Pamplona, Navarra, Spain
* To whom correspondence should be addressed. E-mail: miraburu{at}unav.es.
S-adenosylmethionine (AdoMet) and 5'-Methylthioadenosine (MTA) exert a protective action on apoptosis induced by okadaic acid in primary rat hepatocytes, but not in human transformed HuH7 cells. In the present work we analyzed the role played by the JNK/AP-1 pathway in this differential effect. Okadaic acid induced the phosphorylation of JNK and c-Jun and the binding activity of AP-1 in primary hepatocytes, and pretreatment with either AdoMet or MTA prevented those effects. In HuH7 cells pretreatment with either AdoMet or MTA did not affect JNK and c-Jun activation or AP-1 binding induced by okadaic acid. In both cell types, p38 was activated by okadaic acid, but neither AdoMet nor MTA presented a significant effect on its activity. Therefore, the differential effect of both AdoMet and MTA on the JNK/AP-1 pathway could explain their antiapoptotic effect on primary hepatocytes and the lack of protection they show against okadaic acid-induced apoptosis in hepatoma cells.
