Anne-katrine Kvissel | University of Agder (original) (raw)

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Papers by Anne-katrine Kvissel

Induction of Cbeta splice variants and formation of novel forms of protein kinase A type II holoenzymes during retinoic acid-induced differentiation of human NT2 cells

Cellular signalling, 2004

Cyclic AMP (cAMP) and cAMP-dependent protein kinase (PKA) are critical regulators of neuronal dif... more Cyclic AMP (cAMP) and cAMP-dependent protein kinase (PKA) are critical regulators of neuronal differentiation. The expression, levels and activities of PKA subunits were studied prior to and during differentiation of the human neuronal precursor cell line NTera 2 (NT2). Undifferentiated NT2 cells expressed mainly cytoplasmic PKA type I, consisting of the regulatory subunit RIalpha and the catalytic subunit Calpha. Low levels of PKA type II consisting of RIIalpha or RIIbeta associated with Calpha were also detected, mainly in the cytoplasm and in the Golgi-centrosomal area. During retinoic acid-induced differentiation, the RIalpha and RIIalpha expressions remained in the cytoplasm, while we observed a strong upregulation of RIIbeta, located to the whole cytoplasm including neurite extensions. This upregulation coincided with increased PKA-specific activity accompanied by a strong induction of a number of neuronal-specific Cbeta splice variants that together with RIIbeta form novel PK...

Expression of complement regulators and receptors on human NT2-N neurons—Effect of hypoxia and reoxygenation

Molecular Immunology, 2007

Complement activation can cause tissue damage in cerebral stroke by the release of biologically p... more Complement activation can cause tissue damage in cerebral stroke by the release of biologically potent activation products and impaired function of regulatory proteins. We investigated the constitutive and hypoxia-reoxygenation-dependent expression of complement receptor 1 (CD35), membrane cofactor protein (CD46), decay-accelerating factor (CD55), protectin (CD59), and complement C3a and C5a receptors (C3aR and C5aR) on human NT2-N neurons. The effect of hypoxia-reoxygenation on C3d-deposition on neurons and endothelial cells was also investigated. NT2-N neurons were examined by cellular enzyme-linked immunosorbent assay and immunofluorescence microscopy. Endothelial cells were examined by flow cytometry. Three hours 1% or 0.1% hypoxia and 21h reoxygenation with 50% AB-serum were used to investigate the effect of hypoxia-reoxygenation on regulators and C3d-deposition. NT2-N neurons expressed significant amounts of CD59 (Clone H19/Clone BRIC229: p=0.000006/p=0.000003), CD46 (p=0.00006), CD55 (p=0.003) and C3aR (p=0.00003). CD35 and C5aR were not significantly expressed. There were no effects of hypoxia-reoxygenation on any of the regulators or receptors after 1% hypoxia and reoxygenation. However, CD55 (p=0.02) was down-regulated after 0.1% hypoxia and subsequent reoxygenation with AB-serum. There were no difference observed in the C3d-deposition during hypoxia-reoxygenation in either neurons or endothelial cells. In conclusion, human NT2-N neurons constitutively express C3aR, CD46, CD55 and, in particular, CD59. The cells may respond to locally produced C3a and, at the same time, be well protected against complement attack. Although severe hypoxia-reoxygenation may down-regulate CD55 expression, it does not seem to influence C3d-deposition.

Experimental Cell Research, 2007

Protein kinase A (PKA) is a holoenzyme consisting of two catalytic (C) subunits bound to a regula... more Protein kinase A (PKA) is a holoenzyme consisting of two catalytic (C) subunits bound to a regulatory (R) subunit dimer. Stimulation by cAMP dissociates the holoenzyme and causes translocation to the nucleus of a fraction of the C subunit. Apart from transcription regulation, little is known about the function of the C subunit in the nucleus. In the present report, we show that both Cα and Cβ are localized to spots in the mammalian nucleus.

Protein Kinase A (PKA) - A Potential Target for Therapeutic Intervention of Dysfunctional Immune Cells

Current Drug Targets, 2005

ABSTRACT In several cases of immunodeficiency and autoimmunity, the dysfunctional immune system i... more ABSTRACT In several cases of immunodeficiency and autoimmunity, the dysfunctional immune system is associated with either hypo- or hyperactive T and B cells. In autoimmune conditions such as systemic lupus erythematosus (SLE) and immunodeficiencies such as acquired immunodeficiency syndrome (AIDS), it has been demonstrated that the regulatory effect of the signaling pathway of cyclic 3', 5' adenosine monophosphate (cAMP) and cAMP-dependent protein kinase (PKA) is abrogated. PKA is well-known as a key regulator of immune responses in that it inhibits both early and late phases of antigen induced T and B cell activation. Here we will discuss a potential useful strategy for therapeutic interventions of dysfunctional T cells associated with SLE and HIV by modulation of the cAMP-PKA pathway. Therefore, we will describe the components and architecture of the cAMP-PKA signaling pathway in T cells in order to point out one or several steps which potentially may serve as targets for therapeutic intervention.

Induction of Cβ splice variants and formation of novel forms of protein kinase A type II holoenzymes during retinoic acid-induced differentiation of human NT2 cells

Cellular Signalling, 2004

Brain Research, 2006

Inflammation probably plays a significant role in perinatal brain injury. To study the contributi... more Inflammation probably plays a significant role in perinatal brain injury. To study the contribution of locally produced cytokines, the effect on cell death of addition of IL-8 and MCP-1 or antibodies to these, and the impact of acidosis, human postmitotic NT2-N neurons were exposed to 3 h of hypoxia and glucose deprivation and reoxygenated for 21 h. After 3 h of hypoxia with neutral medium, IL-8 was significantly increased compared to controls (150 (100-250)% vs. 100 (85-115)%, p = 0.023). After 21 h of neutral reoxygenation, both IL-8 (380 (110-710)% vs. 150 (85-260)%, p = 0.041) and monocyte chemoattractant protein-1 (MCP-1) (650 (440-2000)%

BMC Cell Biology, 2008

Background: Epidermal Growth Factor Receptor (EGFR) is a key target molecule in current treatment... more Background: Epidermal Growth Factor Receptor (EGFR) is a key target molecule in current treatment of several neoplastic diseases. Hence, in order to develop and improve current drugs targeting EGFR signalling, an accurate understanding of how this signalling pathway is regulated is required. It has recently been demonstrated that inhibition of cAMP-dependent protein kinase (PKA) induces a ligand-independent internalization of EGFR. Cyclic-AMP-dependent protein kinase consists of a regulatory dimer bound to two catalytic subunits.

BMC Biochemistry, 2011

Background: Protein kinase A type I (PKAI) and PKAII are expressed in most of the eukaryotic cell... more Background: Protein kinase A type I (PKAI) and PKAII are expressed in most of the eukaryotic cells examined. PKA is a major receptor for cAMP and specificity is achieved partly through tissue-dependent expression and subcellular localization of subunits with different biochemical properties. In addition posttranslational modifications help fine tune PKA activity, distribution and interaction in the cell. In spite of this the functional significance of two forms of PKA in one cell has not been fully determined. Here we have tested the ability of PKAI and PKAII formed by expression of the regulatory (R) subunits RIα or RIIα in conjunction with Cα1 or Cβ2 to activate a co-transfected luciferace reporter gene, controlled by the cyclic AMP responsive element-binding protein (CREB) in vivo.

Cellular Signalling, 2007

BACKGROUND. Androgen deprivation is the only effective systemic therapy available for patients wi... more BACKGROUND. Androgen deprivation is the only effective systemic therapy available for patients with prostatic carcinoma, but is associated with a gradual transition to a hormonerefractory prostate cancer (HRCAP) in which ligand-independent activation of the androgen receptor has been implicated. The b 2 -adrenergic receptor (b 2 -AR) is a well-known activator of the androgen receptor. METHODS. Prostatic cell lines were analyzed using cDNA micro-array, real time RT-PCR, radioligand binding assay, cAMP measurements, transfection and thymidine incorporation assay. Clinical specimens were studied by immunohistochemistry and Affymetrix microarrays. RESULTS. Here, we show that b 2 -AR was transiently down-regulated both at mRNA-and protein levels when hormone-sensitive prostate cancer cells, LNCaP, were cultured in steroid stripped medium (charcoal-stripped fetal calf serum) or when the cells were treated with the anti-androgen, bicalutamide (Casodex). The number of b-adrenergic receptors was modestly up-regulated in androgen independent cell lines (LNCaP-C4, LNCaP-C4-2 and DU145) compared to LNCaP. Triiodothyronine (T3) increased the level of b 2 -AR and the effect of T3 was inhibited by bicalutamide. Immunohistochemical staining of human prostate specimens showed high expression of b 2 -AR in glandular, epithelial cells and increased expression in malignant cells compared to benign hyperplasia and normal tissue. Interestingly, b 2 -AR mRNA was strongly down-regulated by androgen ablation therapy of prostate cancer patients. CONCLUSION. The level of b 2 -AR was increased by T3 in prostatic adenocarcinoma cells and reduced in prostate cancer patients who had received androgen ablation therapy for 3 months.