Search results for "kinases"

AMP-activated protein kinase (AMPK) signaling pathway: A potential mechanism involved in PAFIYAMA syndrome?

2016

Cigarette smoke extract activates human bronchial epithelial cells affecting non-neuronal cholinergic system signalling in vitro.

2010

Abstract Aims Acetylcholine (ACh) is synthesized by Choline Acetyl-Transferase (ChAT) that exerts its physiological effects in airway epithelial cells via muscarinic receptor (MR) activation. We evaluate the effect of ACh stimulation on human bronchial epithelial cells (16-HBE) and test whether cigarette smoke extract (CSE) can modify the basal cellular response to ACh affecting the non-neuronal cholinergic system signalling. Main methods ACh stimulated 16-HBE were tested for ACh-binding, Leukotriene B 4 (LTB 4 ) release and ERK1/2 and NFkB pathway activation. Additionally, we investigated all the aforementioned parameters as well as ChAT and MR proteins and mRNA expression and endogenous A…

Neuroendocrine Regulation Of The IL-27-Dependent Immune Response In Macrophages

2013

Abstract The central nervous system has the ability for modulating immune responses, but the molecular mechanisms of such interactions are only partly understood. Interleukin-27 (IL-27) is a heterodimeric protein and structurally related to the IL-12 family of cytokines. IL-27 is composed of the subunits EBI3 and p28. The biological functions of IL-27 have been described as either anti-inflammatory or pro-inflammatory depending on the experimental models studied. In the current study, we investigated how production of Interleukin-27 (IL-27) is regulated by neuroendocrine hormones. We focused our work on the subunit p28, since EBI3 is also present in IL-35 and therefore is not a specific com…

A girl with an atypical form of ataxia telangiectasia and an additional de novo 3.14Mb microduplication in region 19q12

2011

A 9-year-old girl born to healthy parents showed manifestations suggestive of ataxia telangiectasia (AT), such as short stature, sudden short bouts of horizontal and rotary nystagmus, a weak and dysarthric voice, rolling gait, unstable posture, and atactic movements. She did not show several cardinal features typical of AT such as frequent, severe infections of the respiratory tract. In contrast, she showed symptoms not generally related to AT, including microcephaly, profound motor and mental retardation, small hands and feet, severely and progressively reduced muscle tone with slackly protruding abdomen and undue drooling, excess fat on her upper arms, and severe oligoarthritis. A cranial…

Mechanisms of C-reactive protein-induced blood-brain barrier disruption.

2009

Background and Purpose— Increased mortality after stroke is associated with brain edema formation and high plasma levels of the acute phase reactant C-reactive protein (CRP). The aim of this study was to examine whether CRP directly affects blood–brain barrier stability and to analyze the underlying signaling pathways. Methods— We used a cell coculture model of the blood–brain barrier and the guinea pig isolated whole brain preparation. Results— We could show that CRP at clinically relevant concentrations (10 to 20 μg/mL) causes a disruption of the blood–brain barrier in both approaches. The results of our study further demonstrate CRP-induced activation of surface Fcγ receptors CD16/32 fo…

NADPH Oxidase Accounts for Enhanced Superoxide Production and Impaired Endothelium-Dependent Smooth Muscle Relaxation in BKβ1 −/− Mice

2006

Objective— Nitric oxide (NO)-induced vasorelaxation involves activation of large conductance Ca 2+ -activated K + channels (BK). A regulatory BKβ1 subunit confers Ca 2+ , voltage, and NO/cGMP sensitivity to the BK channel. We investigated whether endothelial function and NO/cGMP signaling is affected by a deletion of the β1-subunit. Methods and Results— Vascular superoxide in BKβ1 −/− was measured using the fluorescent dye hydroethidine and lucigenin-enhanced chemiluminescence. Vascular NO formation was analyzed using electron paramagnetic resonance (EPR), expression of NADPH oxidase subunits, the endothelial NO synthase (eNOS), the soluble guanylyl cyclase (sGC), as well as the activity a…

Aberrant copy numbers of ALK gene is a frequent genetic alteration in neuroblastomas.

2009

A total of 50 neuroblastomas were assessed for frequency of ALK gene copy number aberrations by interphase fluorescence in situ hybridization using a break-apart fluorescence in situ hybridization probe. The data were compared with status of MYCN, 11q, 17q, and 1p36. We observed ALK aberrations (amplification, 1 of 45; gain, 15 of 45 and loss/imbalance, 11 of 45) in a total of 27 (60%) of 45 neuroblastomas. Synchronic MYCN and ALK aberrations accounted for 23 of 45 (51%) tumors; however, MYCN alterations were also detected in 11 (60%) of 18 tumors without ALK aberrations. Our data suggest that copy number aberrations of the ALK gene is a frequent genetic event in the development of neurobla…

Ethanol inhibits astroglial cell proliferation by disruption of phospholipase D-mediated signaling.

2002

The activation of phospholipase D (PLD) is a common response to mitogenic stimuli in various cell types. As PLD-mediated signaling is known to be disrupted in the presence of ethanol, we tested whether PLD is involved in the ethanol-induced inhibition of cell proliferation in rat cortical primary astrocytes. Readdition of fetal calf serum (FCS) to serum-deprived astroglial cultures caused a rapid, threefold increase of PLD activity and a strong mitogenic response; both effects were dependent on tyrosine kinases but not on protein kinase C. Ethanol (0.1-2%) suppressed the FCS-induced, PLD-mediated formation of phosphatidic acid (PA) as well as astroglial cell proliferation in a concentration…

Acute estradiol protects CA1 neurons from ischemia-induced apoptotic cell death via the PI3K/Akt pathway

2010

Global ischemia arising during cardiac arrest or cardiac surgery causes highly selective, delayed death of hippocampal CA1 neurons. Exogenous estradiol ameliorates global ischemia-induced neuronal death and cognitive impairment in male and female rodents. However, the molecular mechanisms by which a single acute injection of estradiol administered after the ischemic event intervenes in global ischemia-induced apoptotic cell death are unclear. Here we show that acute estradiol acts via the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling cascade to protect CA1 neurons in ovariectomized female rats. We demonstrate that global ischemia promotes early activation of glycogen syn…

Regulation of the human bradykinin B2 receptor expressed in sf21 insect cells: A possible role for tyrosine kinases

2000

The functional regulation of the human bradykinin B2 receptor expressed in sf21 cells was studied. Human bradykinin B2 receptors were immunodetected as a band of 75–80 kDa in membranes from recombinant baculovirus-infected cells and visualized at the plasma membrane, by confocal microscopy, using an antibody against an epitope from its second extracellular loop. B2 receptors, detected in membranes by [3H-bradykinin] binding, showed a Kd of 0.66 nmol/L and an expression level of 2.57 pmol/mg of protein at 54 h postinfection. In these cells, bradykinin induced a transient increase of intracellular calcium ([Ca2+]i) in fura 2-AM loaded sf21 cells, and promoted [35S]-GTPγS binding to membranes.…