Browsing by Subject "CREB"

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  • Zirnask, Helen; Pollanen, Pasi; Suutre, Siim; Kuuslahti, Marianne; Kotsar, Andres; Pakarainen, Tomi; Kokk, Kersti (2019)
    The aim of this study is to investigate the expression of adenosine 3',5'-cyclic monophosphate (cAMP) and cAMP-response element-binding protein (CREB) in the human penis as it is known that luteinizing hormone (LH) regulates cellular function mostly through the cAMP signaling pathway and LH receptors are expressed by the penile endothelium. Penile tissue was obtained from three patients during partial or total penectomy due to a rectal cancer with secondary penile metastasis or squamous cell carcinoma of the penis. Immunohistochemistry was used for the detection of cAMP and CREB. Positive immunoreaction for cAMP was present in most cells of superficial, intermedial, and basal layer of urethral epithelium and in fibroblast-like cells (FLC) of interstitial tissue and endothelial cells (EC) of cavernous spaces in corpus spongiosum penis. Positive staining for cAMP was also visible in EC of cavernous spaces and in FLC of interstitial tissue in corpus cavernosum penis. Positive immunoreaction for CREB was present in the superficial and intermedial layer of urethral epithelium, and some positive immunoreaction was also noticed in EC of cavernous spaces and in FLC of interstitial tissue in corpus spongiosum penis. Positive staining was also visible in the EC of cavernous spaces and in fibroplast-like cells of the interstitial tissue in the corpus cavernosum penis. Our results show the presence of cAMP and CREB in the human penis. While LH exerts its actions through cAMP signaling system and our previous studies have shown the expression of luteinizing hormone/choriogonadotropin (LHCG) receptor in the mouse and human penis, this finding may support the hypothesis that LH could affect the spongious and cavernous tissue of the human penis and thereby influence the development of erectile dysfunction among aging men.
  • Roussa, Eleni; Speer, Jan Manuel; Chudotvorova, Ilona; Khakipoor, Shokoufeh; Smirnov, Sergei; Rivera Baeza, Claudio; Krieglstein, Kerstin (2016)
    Functional activation of the neuronal K+-Cl- co-transporter KCC2 (also known as SLC12A5) is a prerequisite for shifting GABAA responses from depolarizing to hyperpolarizing during development. Here, we introduce transforming growth factor beta 2 (TGF-beta 2) as a new regulator of KCC2 membrane trafficking and functional activation. TGF-beta 2 controls membrane trafficking, surface expression and activity of KCC2 in developing and mature mouse primary hippocampal neurons, as determined by immunoblotting, immunofluorescence, biotinylation of surface proteins and KCC2-mediated Cl- extrusion. We also identify the signaling pathway from TGF-beta 2 to cAMP-response-element-binding protein (CREB) and Ras-associated binding protein 11b (Rab11b) as the underlying mechanism for TGF-beta 2-mediated KCC2 trafficking and functional activation. TGF-beta 2 increases colocalization and interaction of KCC2 with Rab11b, as determined by 3D stimulated emission depletion (STED) microscopy and co-immunoprecipitation, respectively, induces CREB phosphorylation, and enhances Rab11b gene expression. Loss of function of either CREB1 or Rab11b suppressed TGF-beta 2-dependent KCC2 trafficking, surface expression and functionality. Thus, TGF-beta 2 is a new regulatory factor for KCC2 functional activation and membrane trafficking, and a putative indispensable molecular determinant for the developmental shift of GABAergic transmission.