Bile Acid Regulation of C/EBPβ, CREB, and c-Jun Function, via the Extracellular Signal-Regulated Kinase and c-Jun NH₂-Terminal Kinase Pathways, Modulates the Apoptotic Response of Hepatocytes

Abstract

Previously, we have demonstrated that deoxycholic acid (DCA)-induced signaling of extracellular signalregulated kinases 1 and 2 (ERK1/2) in primary hepatocytes is a protective response. In the present study, we examined the roles of the ERK and c-Jun

Lowering Bile Acid Pool Size with a Synthetic Farnesoid X Receptor (FXR) Agonist Induces Obesity and Diabetes through Reduced Energy Expenditure

“…Besides their well established roles in dietary lipid absorption and cholesterol homeostasis, BAs also function as biological signaling molecules, endowing them with an endocrine function (1). For instance, BAs activate MAPK signaling pathways (2,3) and are natural ligands that activate the nuclear hormone receptor farnesoid X receptor (Fxr, NR1H4) (4 -6), a transcription factor that controls both the biosynthesis and enterohepatic recycling of BAs (7). FXR regulates the expression of the short heterodimer partner (Shp, NR0B2) that inhibits the activity of several other nuclear receptors and contributes to the negative feedback regulation of BA biosynthesis.…”

“…Bile acids (BAs) 3 are essential constituents of bile that facilitate dietary lipid absorption and cholesterol catabolism. Besides their well established roles in dietary lipid absorption and cholesterol homeostasis, BAs also function as biological signaling molecules, endowing them with an endocrine function (1).…”

Signaling pathways regulating intercellular adhesion molecule 1 expression by endothelin 1: Comparison with interleukin‐1β in normal and scleroderma dermal fibroblasts

“…Having identified the importance of NF-B in ET-1-induced ICAM-1 expression, we conclude from these transfection results that binding to the same consensus NF-B site at Ϫ157 bp occurs. ERK-1/2 can also phosphorylate c/EBP␤ (28,29), making it likely that ET-1 exposure leads to a pattern of transcription factor binding similar to that induced by IL-1␤.…”

Effects of ethanol on insulin-like growth factor-I system in primary cultured rat hepatocytes: Implications of JNK1/2 and alcoholdehydrogenase

“…It has been reported that ethanol-induced transient activation of p-JNK1/2 indicates pro-apoptosis, while a prolonged activation induces anti-apoptosis in hepatocytes [20] . Hepatocytes express two JNK genes (JNK1 and JNK2) and bile acids cause activation of both JNK1 and JNK2, but JNK1 activation causes apoptosis whereas JNK2 activation protects against apoptosis [21] . It has been reported that ethanol causes more pronounced activation of JNK 1 compared to JNK 2, suggesting a role for this preferential activation of JNK 1 in ethanol-induced apoptosis of hepatocytes [15] .…”