Search results for "Protein kinase A"

Effects of inhibitors of cGMP-dependent protein kinase in atrial heart and aortic smooth muscle from rats

1995

Several activators of cGMP-dependent protein kinase (protein kinase G) such as 8-Br-cGMP reduced force of contraction in rat left atria. Inhibitors of protein kinase G antagonized the negative inotropic effect of 8-Br-cGMP but not of acetylcholine in atria. However, the acetylcholine-induced relaxation in aortic rings was significantly inhibited by protein kinase G inhibition. It is concluded that the reduction by 8-Br-cGMP of force of contraction in atria is related to activation of protein kinase G. In response to acetylcholine, activation of protein kinase G is probably a major step in smooth muscle relaxation but is not involved in the reduction of force of contraction in atria.

Efavirenz induces alterations in lipid metabolism through AMPK activation

2008

Summary of results EFV produced an immediate reduction of mitochondrialfunction, evident by the significant and dose-dependentinhibition of mitochondrial O2 consumption and thedecrease of intracellular ATP and Δψm. This metabolicstress promoted the activation of AMPK, triggering severalof its signalling pathways, as EFV induced an increment inCD36 mRNA expression and in intracellular lipid content,which could have been a result of the formation of lipiddroplets. This intracellular lipid increase was not presentin cells treated with Compound C, which points to a keyrole for AMPK in these mechanisms. Conclusion Given that EFV treatment is usually prolonged, thesemechanisms may effect the gene…

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…

Regulated Proteolysis of RAGE and AβPP as Possible Link Between Type 2 Diabetes Mellitus and Alzheimer's Disease

2009

Epidemiological studies have linked type 2 diabetes mellitus (T2DM) with an increased risk of developing Alzheimer's disease (AD). In T2DM, the elevated blood glucose level promotes formation of advanced glycation end products (AGEs). The receptor for AGEs (RAGE) is a type I membrane-protein and is also able to import amyloid-beta (Abeta) from the blood across the blood-brain-barrier into the brain. Oligomeric Abeta peptides disturb synaptic function in the brain and are believed to contribute to the development of AD. Abeta peptides are released from the amyloid-beta protein precursor (AbetaPP) after sequential proteolysis by beta- and gamma-secretases but alpha-secretase-mediated cleavage…

Increased Connexin 43 Expression as a Potential Mediator of the Neuroprotective Activity of the Corticotropin-Releasing Hormone

2009

CRH is a major central stress mediator, but also a potent neuroprotective effector. The mechanisms by which CRH mediates its neuroprotective actions are largely unknown. Here, we describe that the gap junction molecule connexin43 (Cx43) mediates neuroprotective effects of CRH toward experimentally induced oxidative stress. An enhanced gap junction communication has been reported to contribute to neuroprotection after neurotoxic insults. We show that CRH treatment up-regulates Cx43 expression and gap junctional communication in a CRH receptor-dependent manner in IMR32 neuroblastoma cells, primary astrocytes, and organotypic hippocampal slice cultures. MAPKs and protein kinase A-cAMP response…

Role of intracellular calcium on ethanol-induced activation of protein kinase A: molecular model and behavioral consequences

2014

Ethanol can be considered a weak drug when compared to most other drugs of abuse. The molecule of ethanol has no asymmetric carbon. Being so, it does not interact with the biological substrates in a stereoselective way as most of the receptor ligand drugs do. Moreover, ethanol has a very simple chemical structure. Thus, the hydroxyl group provides a dipole that allows the formation of hydrogen bonds. It is the formation of hydrogen bonds that makes ethanol soluble in water. In contrast, ethanol presents an aliphatic moiety that provides a lipophilic group that can interact with non-polar cellular elements. However, contrary to what it is generally believed, ethanol has low lipid solubility.…

Targeting GSK3 and Associated Signaling Pathways Involved in Cancer

2020

Glycogen synthase kinase 3 (GSK-3) is a serine/threonine (S/T) protein kinase. Although GSK-3 originally was identified to have functions in regulation of glycogen synthase, it was subsequently determined to have roles in multiple normal biochemical processes as well as various disease conditions. GSK-3 is sometimes referred to as a moonlighting protein due to the multiple substrates and processes which it controls. Frequently, when GSK-3 phosphorylates proteins, they are targeted for degradation. GSK-3 is often considered a component of the PI3K/PTEN/AKT/GSK-3/mTORC1 pathway as GSK-3 is frequently phosphorylated by AKT which regulates its inactivation. AKT is often active in human cancer a…

Activation of the p38MAPK cascade is associated with upregulation of TNF alpha receptors in the spinal motor neurons of mouse models of familial ALS.

2005

Phosphorylated p38 mitogen-activated protein kinase (p38MAPK), but not activated c-jun-N-terminal kinase (JNK), increases in the motor neurons of transgenic mice overexpressing ALS-linked SOD1 mutants at different stages of the disease. This effect is associated with a selective increase of phosphorylated MKK3-6, MKK4 and ASK1 and a concomitant upregulation of the TNFalpha receptors (TNFR1 and TNFR2), but not IL1beta and Fas receptors. Activation of both p38 MAPK and JNK occurs in the activated microglial cells of SOD1 mutant mice at the advanced stage of the disease; however, this effect is not accompanied by the concomitant activation of the upstream kinases ASK1 and MKK3,4,6, while both …

Protein Phosphorylation by Peroxisome Proliferators: Species-specific Stimulation of Protein Kinases and Its Role in PP-induced Transcriptional Activ…

1996

Molecular mechanisms of MYCN-dependent apoptosis and the MDM2-p53 pathway: an Achille’s heel to be exploited for the therapy of MYCN amplified neurob…

2012

The p53 oncosuppressor is very seldom mutated in neuroblastoma, but several mecha- nisms cooperate to its functional inactivation in this tumor. Increased MDM2 levels, due to genetic amplification or constitutive inhibition of p14ARF, significantly contribute to this event highlighting p53 reactivation as an attractive perspective for neuroblastoma treat- ment. In addition to its role in tumorigenesis, MYCN sensitizes untransformed and cancer cells to apoptosis. This is associated to a fine modulation of the MDM2-p53 pathway Indeed MYCN induces p53 and MDM2 transcription, and, by evoking a DNA damage response (DDR), it stabilizes p53 and its proapoptotic kinase Homeodomain Interacting Prote…