The Experts below are selected from a list of 240 Experts worldwide ranked by ideXlab platform

Alberto M Martelli - One of the best experts on this subject based on the ideXlab platform.

  • the nuclear phosphoinositide 3 kinase akt pathway a new Second Messenger System
    Biochimica et Biophysica Acta, 2002
    Co-Authors: Luca M Neri, Paola Borgatti, Silvano Capitani, Alberto M Martelli
    Abstract:

    Lipid Second Messengers, particularly those derived from the polyphosphoinositide cycle, play a pivotal role in several cell signaling networks. Phosphoinositide 3-kinases (PI3Ks) generate specific inositol lipids that have been implicated in a plethora of cell functions. One of the best-characterized targets of PI3K lipid products is the serine/threonine protein kinase Akt. Recent findings have implicated Akt in cancer progression because it stimulates cell proliferation and suppresses apoptosis. Evidence accumulated over the past 15 years has highlighted the presence of an autonomous nuclear inositol lipid metabolism, and suggests that lipid molecules are important components of signaling pathways operating within the nucleus. PI3Ks, their lipid products, and Akt have also been identified at the nuclear level. In this review, we shall summarize the most updated findings about these molecules in relationship with the nuclear compartment and provide an overview of the possible mechanisms by which they regulate important cell functions.

Richard S Jope - One of the best experts on this subject based on the ideXlab platform.

  • phosphoinositide hydrolysis gαq phospholipase c and protein kinase c in post mortem human brain effects of post mortem interval subject age and alzheimer s disease
    Neuroscience, 1995
    Co-Authors: Angela F Greenwood, Richard E Powers, Richard S Jope
    Abstract:

    Abstract Influences of post mortem time interval, subject age and Alzheimer's disease were investigated on several components of the phosphoinositide Second Messenger System, including stimulation of [ 3 H]phosphatidylinositol hydrolysis by GTP[S] and several receptor agonists and the levels of Gαq, β, δ and γ subtypes of phospholipase C, and five protein kinase C isoforms, in membranes prepared from post mortem human prefrontal cortex. Most of these components were stable with post mortem delays in the range of 5–21 h, but decreases of Gαq and the α and ζ protein kinase C subtypes were detected. Within the subject age range of 19–100 years, G-protein- and agonist-induced [ 3 H]phosphatidylinositol hydrolysis decreased, as did levels of Gαq, but the levels of phospholipase C and protein kinase C subtypes were generally unchanged. In Alzheimer's disease, compared with age- and post mortem interval-matched controls, there was a decrease in [ 3 H]phosphatidylinositol hydrolysis stimulated by G-proteins and by several receptor agonists, but the levels of Gαq and most of the phospholipase C and protein kinase C isoforms were unaffected. The greatest deficits, which were >50%, occurred with GTP[S]- and carbachol-induced [ 3 H]phosphatidylinositol hydrolysis, indicating that this G-protein function and the response to cholinergic stimulation are significantly impaired in Alzheimer's disease. In summary a comprehensive assessment of several components of the phosphoinositide Second Messenger System was made in post mortem human brain. Most elements were stable within the post mortem interval range of 5–21 h, lending validity to measurements using these tissues. Significant age-related reductions in several components were identified, indicating loss of responses with increasing age. Most importantly, severe reductions in responses to several stimuli were found in Alzheimer's disease brain, deficits in signal transduction which may contribute to impaired cognition and to the limited therapeutic responses to drugs, such as those used to activate cholinergic receptors coupled with the phosphoinositide System.

Masahiro Fujita - One of the best experts on this subject based on the ideXlab platform.

  • effects of camp dependent protein kinase activator and inhibitor on in vivo rolipram binding to phosphodiesterase 4 in conscious rats
    Synapse, 2010
    Co-Authors: Tetsuji Itoh, Kohji Abe, Jinsoo Hong, Osamu Inoue, Victor W Pike, Robert B Innis, Masahiro Fujita
    Abstract:

    Rolipram is a selective inhibitor of phosphodiesterase-4 (PDE4), and positron emission tomography (PET) using [(11)C]rolipram can monitor the in vivo activity of this enzyme that is part of the cAMP Second Messenger cascade. cAMP-dependent protein kinase (PKA) phosphorylates PDE4 and increases both enzyme activity and affinity for rolipram. In the present PET study, we examined effects of PKA modulators in conscious rats on the binding of [(11)C](R)-rolipram in comparison to the much less active enantiomer [(11)C](S)-rolipram. Unilateral injection of a PKA activator (dibutyryl-cAMP) and a PKA inhibitor (Rp-adenosine-3',5'-cyclic monophosphorothioate) into the striatum significantly increased and decreased, respectively, the binding of [(11)C](R)-rolipram. These effects were not caused by changes in blood flow or delivery of radioligand to brain, since these agents had no effect on the binding of [(11)C](S)-rolipram binding. These results support the value of measuring in vivo [(11)C](R)-rolipram binding in brain to assess responses to physiological or pharmacological challenges to the cAMP Second Messenger System.

Kohji Abe - One of the best experts on this subject based on the ideXlab platform.

  • effects of camp dependent protein kinase activator and inhibitor on in vivo rolipram binding to phosphodiesterase 4 in conscious rats
    Synapse, 2010
    Co-Authors: Tetsuji Itoh, Kohji Abe, Jinsoo Hong, Osamu Inoue, Victor W Pike, Robert B Innis, Masahiro Fujita
    Abstract:

    Rolipram is a selective inhibitor of phosphodiesterase-4 (PDE4), and positron emission tomography (PET) using [(11)C]rolipram can monitor the in vivo activity of this enzyme that is part of the cAMP Second Messenger cascade. cAMP-dependent protein kinase (PKA) phosphorylates PDE4 and increases both enzyme activity and affinity for rolipram. In the present PET study, we examined effects of PKA modulators in conscious rats on the binding of [(11)C](R)-rolipram in comparison to the much less active enantiomer [(11)C](S)-rolipram. Unilateral injection of a PKA activator (dibutyryl-cAMP) and a PKA inhibitor (Rp-adenosine-3',5'-cyclic monophosphorothioate) into the striatum significantly increased and decreased, respectively, the binding of [(11)C](R)-rolipram. These effects were not caused by changes in blood flow or delivery of radioligand to brain, since these agents had no effect on the binding of [(11)C](S)-rolipram binding. These results support the value of measuring in vivo [(11)C](R)-rolipram binding in brain to assess responses to physiological or pharmacological challenges to the cAMP Second Messenger System.

Kyuya Kogure - One of the best experts on this subject based on the ideXlab platform.

  • autoradiographic distribution of neurotransmitter and Second Messenger System receptors in animal brains
    Behavioural Brain Research, 1994
    Co-Authors: Yasuo Kanai, Tsutomu Araki, Hiroyuki Kato, Kyuya Kogure
    Abstract:

    Abstract We investigated species difference in binding of major neurotransmitters and intracellular Second Messengers in the gerbil brain and the rat brain using receptor autoradiography. [ 3 H]Phorbol 12,13-dibutyrate (PDBu), [ 3 H]inositol 1,4,5-trisphosphate (IP 3 ), [ 3 H]PN200-110, [ 3 H]muscimol, [ 3 H]MK-801, [ 3 H]cyclohexyladenosine (CHA), and [ 3 H]quinuclidinyl benzilate (QNB) were used to label protein kinase C, IP 3 receptor, L-type calcium channel, γ-aminobutyric acid A (GABA A ) receptor, N -methyl-D-aspartate (NMDA) receptor, adenosine A 1 receptor, and muscarinic cholinergic receptor, respectively. Autoradiographic distributions of the bindings of most neurotransmitters and Second Messengers were particularly found in the limbic System and basal ganglia in both gerbil and rat brains. However, marked differences in these bindings between the gerbil brain and the rat brain were also recognized in the above regions. In particular, among 7 ligands used, the gerbil had high [ 3 H]PDBu and [ 3 H]CHA binding sites throughout the brain compared to those in the rat brain except for a few areas. By contrast, the rat exhibited high [ 3 H]MK-801 binding sites in various brain regions, as compared with the gerbil brain. Thus, the gerbil differ from the rat with respect to the binding sites of major Second Messengers and neurotransmitters in the brain. The results may help better elucidate the relationship or species difference between gerbils and rats for neuronal function and behavioral pharmacology.

  • Phospholipid metabolism and Second Messenger System after brain ischemia.
    Advances in experimental medicine and biology, 1992
    Co-Authors: Koji Abe, Tsutomu Araki, J. Kawagoe, Masashi Aoki, Kyuya Kogure
    Abstract:

    To evaluate possible involvement of phospholipid metabolism and related Second Messenger Systems in the selective neuronal damage after ischemia, we measured changes of polyphosphoinositides (PPIs) and free fatty acids (FFAs) in a model of 5-min or 10-min ischemia and reperfusion in gerbils. The binding activity of 3H-phorbol 12, 13-dibutyrate (PDBu) for protein kinase C (PKC) and 3H-inositol 1,4,5-triphosphate (IP3) for IP3 receptors was demonstrated autoradiographically. Induction of 70 KDa heat shock protein (HSP70) mRNA and amyloid precursor protein (APP) mRNA was also examined using Northern blot analysis.