Selective β2 adrenergic agonist increases Cx43 and miR-451 expression via cAMP-Epac

Abstract

Abstract. It has been demonstrated that connexin 43 (Cx43) and microRNAs have significant roles in glioma. Cyclic adenosine monophosphate (cAMP) is suggested to be a regulator of connexins and microRNAs. However, it remains elusive whether cAMP and exchange protein directly activated by cAMP (Epac2), have a regulatory effect on Cx43 and microRNA-451 (miR-451) in astrocytoma cells. We treated 1321N1 astrocytoma cells with a selective β2 adrenergic agonist and a selective Epac activator with and without adenyl cyclase and protein kinase A inhibition. Cx43 and miR-451 expression were measured. Next, we evaluated the effect of miR-451 overexpression on Cx43 expression. Cell proliferation was measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results demonstrated that cAMPEpac2 increased Cx43 and miR-451 expression. However, the alteration of miR-451 expression required a higher dose of drugs. Overexpression of miR-451 had no significant effect on Cx43 expression. The MTT assay showed that cAMP-Epac stimulation and miR-451 overexpression had a synergic inhibitory effect on cell proliferation. These findings may expand our understanding of the molecular biology of glioma and provide new potential therapeutic targets.

Epac1 is involved in cell cycle progression in lung cancer through PKC and Cx43 regulation

“…In the present study, significant correlations between Epac1 and PKC immunoreactivity on one hand, and between Epac1 and Cx43 immunoexpression on the other hand, were observed in lung cancer tissues, indicating that Epac1 may be involved in the regulation of lung cancer cell proliferation through the PKC and Cx43 proteins. These findings were consistent with previous reports [28,29].…”

“…It was shown that Epac can induce PKC activation and Cx43 phosphorylation [28]. The complex cAMP-Epac2 increases Cx43 expression, and Epac2 overexpression inhibits glioma cell proliferation [29]. In the present study, significant correlations between Epac1 and PKC immunoreactivity on one hand, and between Epac1 and Cx43 immunoexpression on the other hand, were observed in lung cancer tissues, indicating that Epac1 may be involved in the regulation of lung cancer cell proliferation through the PKC and Cx43 proteins.…”

miR-125a, miR-139 and miR-324 contribute to Urocortin protection against myocardial ischemia-reperfusion injury

“…In contrast, little is known about Epac2 regulation of miRNAs in the heart. Recent studies indicated that Epac modulated the expression of miRNAs in other cell types, as it is the case of miR-20 in macrophages 27 , and miR-451 in astrocytoma cells 28 .…”

Myocardial electrotonic response to submaximal exercise in dogs with healed myocardial infarctions: evidence for β-adrenoceptor mediated enhanced coupling during exercise testing

“…On the other hand, susceptible animals also exhibit enhanced cardiac β-AR responsiveness, presenting a dominant functional contribution of the β 2 -adrenergic receptors following MI, both in vivo and in vitro (Billman et al, 1997 ; Houle et al, 2001 ). Notably, acute β 2 -AR stimulation can increase junctional conductance and protein expression in cardiac myocytes (Xia et al, 2009 ), likely via the exchange protein directly activated by cAMP (Epac)/Rap1 signaling pathway (Somekawa et al, 2005 ; Duquesnes et al, 2010 ; Mostafavi et al, 2014 ).…”