The Bile Acid Tauroursodeoxycholic Acid Modulates Phosphorylation and Translocation of Bad via Phosphatidylinositol 3-Kinase in Glutamate-Induced Apoptosis of Rat Cortical Neurons

Abstract

Neurotoxicity associated with increased glutamate release results in cell death through both necrotic and apoptotic processes. In addition, tauroursodeoxycholic acid (TUDCA), an endogenous bile acid, is a strong modulator of apoptosis in several cell types. The aims of this study were to test the hypothesis that TUDCA reduces the apoptotic threshold induced by glutamate in rat cortical neurons and examine potential transduction pathways involved in both apoptotic signaling and neuroprotection by TUDCA. The results demonstrated that exposure of cortical neurons to glutamate induced cytochrome c release and caspase activation, as well as morphologic changes of apoptosis. These events were associated with down-regulation of antiapoptotic members of the Bcl-2 family,

Tauroursodeoxycholic acid inhibits apoptosis induced by Z alpha-1 antitrypsin via inhibition of bad

“…30 Bad is known to be dephosphorylated and activated in primary cortical neurons treated with the ER stressors, whereas resistance to ER-mediated apoptosis in murine chronic myeloid leukemic cells involves persistent phosphorylation and inactivation of Bad. 12,31 TUDCA can increase p-Bad and enhance survival in neuronal cells, and our findings show that a similar mechanism occurs in HEK293 cells expressing ZAAT, promoting cell survival via release of Bcl-2 and Bcl-X L from Bad. This is consistent with overexpression of Bcl-X L , which can inhibit ER stress-induced apoptosis.…”

Tauroursodeoxycholic acid reduces endoplasmic reticulum stress, acinar cell damage, and systemic inflammation in acute pancreatitis

“…The release of cytochrome c from mitochondria downstream of the caspase activation should be investigated in future studies because it is important in AP (42). Beyond that, TUDCA is able to phosphorylate cyclic adenosine monophosphateϭresponsive element-binding protein and activates phosphatidylinositol 3-kinase-dependent Bad signaling as demonstrated earlier (10,63).…”

Bile acids: regulation of apoptosis by ursodeoxycholic acid

“…Interestingly, pretreatment with TUDCA also signifi cantly reduced glutamate-induced apoptosis of rat cortical neurons. TUDCA was capable of modulating glutamate-induced caspase activation and cytochrome c release, reducing the apoptotic threshold ( 136 ).…”