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Catecholamines regulate the b-adrenoceptor/cyclic AMP-regulated protein kinase A (cAMP/PKA) pathway. Deregulation of this pathway can cause apoptotic cell death and is implicated in a range of human diseases, such as neuronal loss during aging, cardiomyopathy and septic shock. The molecular mechanism of this process is, however, only poorly understood. Here we demonstrate that the b-adrenoceptor/cAMP/PKA pathway triggers apoptosis through the transcriptional induction of the pro-apoptotic BH3-only Bcl-2 family member Bim in tissues such as the thymus and the heart. In these cell types, the catecholamine-mediated apoptosis is abrogated by loss of Bim. Induction of Bim is driven by the transcriptional co-activator CBP (CREB-binding protein) together with the proto-oncogene c-Myc. Association of CBP with c-Myc leads to altered histone acetylation and methylation pattern at the Bim promoter site. Our findings have implications for understanding pathophysiology associated with a deregulated neuroendocrine system and for developing novel therapeutic strategies for these diseases. Cell Death and Differentiation (2013) 20, 941-952; doi:10.1038/cdd.2013 published online 12 April 2013 Cyclic adenosine monophosphate (cAMP) is a second messenger that is highly conserved throughout evolution. In metazoans, its primary role is to act as an intracellular carrier of metabolic information, regulating hormonal responses, 1 in triggering apoptotic cell death and in regulating ontogeny.2,3

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Our findings indicate a remarkable improvement in most of the health indicators in rural areas. On the other hand, there is still considerable inequality among the rural population at a provincial level.