Differential regulation of the JNK/AP-1 pathway by S-adenosylmethionine and methylthioadenosine in primary rat hepatocytes versus HuH7 hepatoma cells

被引:10
作者
Ansorena, Eduardo
Berasain, Carmen
Zabalza, Marin J. Lopez
Avila, Matias A.
Garcia-Trevijano, Elena R.
Iraburu, Maria J.
机构
[1] Univ Navarra, Dept Bioquim & Biol Mol, Pamplona, Spain
[2] Univ Navarra, Ctr Invest Med Aplicada, Area Hepatol & Terapia Genica, Pamplona, Spain
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2006年 / 290卷 / 06期
关键词
okadaic acid; c-Jun; apoptosis; activator protein-1;
D O I
10.1152/ajpgi.00282.2005
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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/activator protein (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.
引用
收藏
页码:G1186 / G1193
页数:8
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