Induction of LRF-1/ATF3 by Vasopressin in Hepatocytes: Role of MAP Kinases

Cellular Physiology and Biochemistry

关键词: LRF-1/ATF3;    Hepatocytes;    G protein-coupled receptors;    Vasopressin;    Ca2+;    Mitogen-activated protein kinases;   

DOI  :  10.1159/000303056

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims Liver regeneration factor 1 (LRF-1/ATF3) is an early response gene which is rapidly induced upon partial hepatectomy in rats, and by growth factors and G protein-coupled receptor (GPCR) agonists in cultured rat hepatocytes. The aim of the present study was to examine the mechanisms involved in induction of LRF-1/ATF3 by the GPCR agonist vasopressin. Methods Primary cultures of rat hepatocytes were treated with vasopressin, TPA, and the Ca²⁺-elevating agents thapsigargin and A23187. LRF-1/ATF3 mRNA and protein were measured by Northern blot analysis or RT-PCR and immunoblotting. Signalling pathways were examined by immunoblots and kinase assays. Results While elevation of intracellular calcium induced LRF-1/ATF3 expression, treatment with TPA did not. Inhibition of phospholipase C, protein kinase C, or pretreatment with calcium chelators did not affect vasopressin-induced expression of LRF-1/ATF3. Inhibition of each of the MAP kinases ERK1/2, JNK or p38 did not affect vasopressin-induced LRF-1/ATF3 expression. Combined inhibition of JNK and p38, and of ERK1/2 and either JNK or p38 suppressed vasopressin-induced expression of LRF-1/ATF3. Conclusion Vasopressin induces LRF-1/ATF3 expression by mechanisms that differ from those activated by Ca²⁺-elevating agents. The results suggest that partly redundant, complex MAP kinase networks are involved in induction of LRF-1/ATF3 by vasopressin in hepatocytes.

【 授权许可】

CC BY-NC-ND