Cyclic AMP response element binding protein CREB

But how do changes in monoamine transmitter levels produce an eventual elevation of mood Raised neurotransmitter concentrations produce immediate alterations in postsynaptic receptor activation, leading to changes in second messenger (intracellular) systems and to gradual modifications in cellular protein expression. Antidepressants increase a cyclic AMP response-element binding (CREB) protein which in turn is involved in... 

Noradrenaline acts on three types of receptor. The ai receptors mediate the main excitatory effects of noradrenaline upon wake-active neurons in the dorsal raphe, basal forebrain, and elsewhere (Vandermaelen Aghajanian, 1983 Nicoll, 1988 Fort et al., 1995 Brown et al., 2002). The a2 receptors mediate inhibitory effects of noradrenaline, e.g. on noradrenaline neurons themselves and on cholinergic brainstem neurons (Williams et al., 1985 Williams Reiner, 1993). The (3-receptors modulate neurons in a more subtle fashion, increasing excitability via blockade of afterhyperpolarizations in hippocampal and cortical neurons (Haas Konnerth, 1983). Activation of (3-receptors also promotes synaptic plasticity via activation of the cyclic-AMP-dependent kinase (PKA) and cyclic AMP response element binding protein (CREB) signal transduction pathway (Stanton Sarvey, 1987 Cirelli et al., 1996). 

CREB cyclic AMP response element binding protein... 

FIGURE 35-6 Examples of apoptotic and antiapoptotic mechanisms that act on or within different subcellular compartments. CBP, Ca2+ binding protein CREB, cyclic AMP response element binding protein HSP, heat shock protein IP3, inositol 1,4,5-trisphosphate ROS, reactive oxygen species. 

An example of specific transcriptional control is cyclic AMP-dependent regulation of genes that have a cyclic AMP response element (CRE) through the action of the transcription factor CREB (cyclic AMP response element binding protein. Figure 12-5). 

BNST, bed nucleus of the stria terminalis CREB, cyclic AMP response element-binding protein CRH, corticotrophin-releasing hormone CS, conditioned stimuH GABA, y-aminobutyric acid GCC, voltage-gated calcium channels NE, norepinephrine NMDA, iST-methyl-D-aspartate PAG, periaqueductal gray. 

Figure 31.24. Coactivator Structure. The pi60 family of coactivators includes a number of domains that can be recognized at the amino acid sequence level, including a basic helix-loop-helix domain that takes part in DNA binding, a PAS domain that participates in protein-protein interactions, a central domain that contacts the ligandbinding domain of the nuclear hormone receptors, and a domain that interacts with additional coactivators such as p300 and CREB-binding protein (CBP). (CREB stands for cyclic AMP-response element binding protein.) The nuclear hormone receptor interaction domain includes three Leu-X-X-Leu-Leu sequences.

Figure 31.31. Cyclic AMP-Response Element Binding Protein (CREB). Each of two CREB subunits contributes a long a helix. The two helices coil around each other to form a dimeric DNA-binding unit. CREB is phosphorylated on a specific serine residue by protein kinase A.

Warwick HK, Nahorski SR, Challiss RA (2005) Group I metabotropic glutamate receptors, mGlula and mGlu5a, couple to cyclic AMP response element binding protein (CREB) through a common Ca2+ - and protein kinase C-dependent pathway. J Neurochem... 

Many inflammatory cytokines including IL-8 are regulated at transcriptional levels, and a variety of transcription factors such as nuclear factor-K B (NFkB) and activator protein-1 (AP-1) play important roles in such processes. Abe and coworkers [71] demonstrated that CAM repressed TNF-a-induced AP-1 activation in human bronchial epithelial cells. We studied the effect of EM and CAM on the phorbol myristate acetate (PMA)-induced activation of NFkB and AP-1. Pretreatment of EM and CAM before the PMA treatment showed an inhibitory effect on both of the transcription factors as assessed by electrophoretic mobility shift assay (EMSA) (Fig. 14) [20]. In contrast, the macrolides showed no effect on the activation of cyclic AMP-responsive element binding protein (CREB), suggesting that the suppressive effect on some transcription factors is specific. We further evaluated the effect of EM on the phosphorylation of inhibitor of NFkB (IkB), which is a crucial step for transactivation of NFkB. EM did not influence the phosphorylation processes in vitro (Okazaki et at, unpublished data, January 2001). These data suggest that EM acts at the process of nuclear translocation of... 

Tuttolomondo A, Di Raimondo D, di Sciacca R, Pinto A, Licata G (2008) Inflammatory cytokines in acute ischemic stroke. CurrPharm Des 14 3574-3589 van Wijk SJ, Haegeman GJ (2005) Poly(ADP-ribose) polymeiase-1 mediated caspase-independent cell death after ischemia/reperfusion. Free Rad Biol Med 39 81-90 Walton M, Siiimanne E, Williams C, Gluckman P, Dragunow M (1996) The role of the cyclic AMP-responsive element binding protein (CREB) in hypoxic-ischemic brain damage and repair. Brain Res Mol Brain Res 43 21-29... 

---