Dibutyryl cyclic AMP induces differentiation of human neuroblastoma SH-SY5Y cells into a noradrenergic phenotype

Effects of Gc-Macrophage Activating Factor in Human Neurons; Implications for Treatment of Chronic Fatigue Syndrome

“…After incubation with GcMAF, the cells appeared to establish contacts with each other. Taken together these results indicate that GcMAF at pM concentration increases neuronal cell viability, metabolic activity and differentiation, with the first effects being observed at 24 h. Considering the well demonstrated role of cAMP in the induction of SH-SY5Y differentiation (Kume et al, 2008), it can be hypothesized that these effects of GcMAF are mediated by the cAMP signalling pathway involving the Extracellular signal-Regulated protein Kinase (ERK) and the nuclear factor kappa B (NF-κB) pathways (Sun et al, 2012). As it was recently demonstrated, this latter signalling pathway is strictly interconnected with the VDR signalling pathway in human mononuclear cells (Nakou et al, 2010), thus lending credit to the hypothesis that the effects of GcMAF are due to a complex, interconnected, network of intracellular signalling.…”

Transcriptomic Profiling Discloses Molecular and Cellular Events Related to Neuronal Differentiation in SH-SY5Y Neuroblastoma Cells

“…All trans retinoic acid (RA), a vitamin A metabolite involved in growth and development, is known to induce neuronal differentiation of SH-SY5Y cells as well as to inhibit the cellular proliferation (Borriello et al 2006;Cheung et al 2009;Constantinescu et al 2007;Cuende et al 2008;Nakamura et al 2003;Pahlman et al 1984). A more mature neuronal phenotype can be reached using growth medium supplemented with specific chemical factors, such as recombinant human brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), dibutyryl-cyclic AMP (db-cAMP), phorbol esters and others (Agholme et al 2010;Dwane et al 2013;Encinas et al 2000;Gimenez-Cassina et al 2006;Jamsa et al 2004;Kou et al 2008;Kume et al 2008;Sarkanen et al 2007). Thereafter, SH-SY5Y cells have been largely utilized to investigate the disease mechanisms associated with various neurodegenerative disorders (Agholme et al 2014;Ferreira et al 2013;Hadzhieva et al 2013;Jamsa et al 2004;Ke et al 2012;Krishna et al 2014;Lim et al 2015;Lopes et al 2010Lopes et al , 2012Palomo et al 2011;Scifo et al 2013Scifo et al , 2015.…”

Sympathetic Neurotransmitters in Neuroblastoma – Between Physiology and Pathology

“…The most extensively studied is retinoic acid and its derivatives, which have been recently introduced to the clinic as a routine treatment following chemotherapy (Handler et al, 2000;Maris, 2010;Sidell, 1982). Similar effects, however, can also be achieved with other factors, such as NGF in neuroblastoma cells with induced TrkA receptor expression, nitric oxide and cyclic AMP (cAMP) -stimulating factors, such as prostaglandins and pituitary adenylate cyclase activating polypeptide (PACAP), as well as a stable analog of cAMP, dibutyryl cAMP (Kume et al, 2008;Matsushima & Bogenmann, 1990;Monaghan et al, 2008;Prasad et al, 2003;Revoltella & Butler, 1980;Reynolds & Perez-Polo, 1981;Rodriguez-Martin et al, 2000) (Fig. 1).…”

“…1). Depending on the type of differentiation factor and cell line used, such a morphological differentiation is associated with augmenting the adrenergic features of the cells manifested by increase in norepinephrine synthesis or, conversely, in down-regulation of adrenergic markers and enhancement of cholinergic properties (Handler et al, 2000;Kume et al, 2008;Pahlman et al, 1981). In some cases, stimulation of the mixed adrenergic and cholinergic phenotype has been observed (Monaghan et al, 2008).…”