Alpha-2-macroglobulin Homologues Mediating Nerve Degeneration And Regeneration
Biochemistry & Molecular Biology; Cell Biology; Life Sciences & Biomedicine - Other; Topics
Lee P G; Hu Y Q; Liebl D J; Koo P H
Faseb Journal
1997
1997-07
Journal Article or Conference Abstract Publication
n/a
Monoamine-activated Alpha(2)-macroglobulin Inhibits Neurite Outgrowth, Survival, Choline-acetyltransferase, And Dopamine Concentration Of Neurons By Blocking Neurotrophin-receptor (trk) Phosphorylation And Signal-transduction
alpha(2)-macroglobulin; alpha-macroglobulin; nerve growth-factor
Koo P H; Liebl D J; Qiu W S; Hu Y Q; Dluzen D E
Biology of Alpha2-Macroglobulin, Its Receptor, and Related Proteins
1994
1994
Book Chapter
<a href="http://doi.org/10.1111/j.1749-6632.1994.tb44340.x" target="_blank" rel="noreferrer noopener">10.1111/j.1749-6632.1994.tb44340.x</a>
Inhibition Of Phosphorylation Of Trkb And Trkc And Their Signal Transduction By Alpha(2)-macroglobulin
alpha(2)-macroglobulin; alpha(2)-macroglobulin; alpha(2)-macroglobulin; Alzheimer's disease; Biochemistry & Molecular Biology; cerebrospinal-fluid; dopaminergic-neurons; mitogen-activated protein kinases; nerve growth-factor; neurite outgrowth; Neurodegenerative diseases; Neurosciences & Neurology; neurotrophic factor; neurotrophins; phospholipase C-gamma 1; rat caudate-putamen; signal-transduction; tyrosine protein-kinase
Monoamine-activated alpha(2)-macroglobulin (alpha(2)M) was shown to reduce the dopamine concentration in corpus striatum of adult rat brains and inhibit other neuronal functions in vivo and in vitro. As brain-derived neurotrophic factor, neurotrophin-4, and neurotrophin-3 are important neurotrophic factors for dopaminergic neurons, the effect of monoamine-activated alpha(2)M on signal transduction by trkB and trkC was investigated. The results show that monoamine-activated alpha(2)M binds to trkB and inhibits brain-derived neurotrophic factor/neurotrophin-4-promoted autophosphorylation of trkB in a dose-dependent manner in both trkB-expressing NIH3T3 (NIH3T3-trkB) and human neuroblastoma SH-SY5Y cells. Monoamine-activated alpha(2)M also blocks tyrosine phosphorylation of phospholipase C-gamma 1 and extracellular signal-regulated protein kinase(ERK)-1,which are key intracellular proteins involved in trkB signal transduction. Similarly, monoamine-activated alpha(2)M inhibits tyrosine phosphorylation of neurotrophin-3-induced trkC and its signal transduction in a dose-dependent manner in NIH3T3 cells expressing trkC (NIH3T3-trkC). In contrast to monoamine-activated alpha(2)M, normal alpha(2)M has little or no significant inhibitory effect on the phosphorylation of trkB and trkC. In addition, the retinoic acid-promoted tyrosine phosphorylation of phospholipase C-gamma 1, ERK-1, and/or ERK-2 in SH-SY5Y cells was unaffected by monoamine-activated alpha(2)M; this suggests that the inhibitory effect of activated alpha(2)M on the neurotrophin-stimulated phosphorylation of intracellular signalling proteins may be specific. Taken together, the data indicate that activated alpha(2)M is a pan-trk inhibitor, which by virtue of its binding to trk receptors may block trk-mediated signal transduction in dopaminergic neurons and lead to reduction of dopamine concentration in corpus striatum.
Hu Y Q; Koo P H
Journal of Neurochemistry
1998
1998-07
Journal Article or Conference Abstract Publication
n/a
Monoamine-activated alpha 2-macroglobulin inhibits neurite outgrowth, survival, choline acetyltransferase, and dopamine concentration of neurons by blocking neurotrophin-receptor (trk) phosphorylation and signal transduction.
Humans; Animals; Cell Survival/drug effects; Phosphorylation/drug effects; Signal Transduction/*drug effects; Infant; Neurons/physiology; Rats; Species Specificity; Choline O-Acetyltransferase/metabolism; Dopamine/metabolism; alpha-Macroglobulins/*pharmacology; Biogenic Monoamines/*pharmacology; Neurites/physiology; Prosencephalon/cytology/*physiology; Receptor Protein-Tyrosine Kinases/*drug effects; Newborn; Receptors; Nerve Growth Factor/*drug effects
Koo P H; Liebl D J; Qiu W S; Hu Y Q; Dluzen D E
Annals of the New York Academy of Sciences
1994
1994-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Inhibition of phosphorylation of TrkB and TrkC and their signal transduction by alpha2-macroglobulin.
Humans; Animals; Mice; Signal Transduction/drug effects/*physiology; Phosphorylation; Mitogen-Activated Protein Kinase 1/metabolism; Antineoplastic Agents/pharmacology; Type C Phospholipases/metabolism; Cell Differentiation/drug effects; Neuroprotective Agents/*metabolism; Neuroblastoma; alpha-Macroglobulins/*pharmacology; *Mitogen-Activated Protein Kinases; 3T3 Cells/chemistry/cytology/enzymology; Brain-Derived Neurotrophic Factor/pharmacology; Calcium-Calmodulin-Dependent Protein Kinases/metabolism; Isoenzymes/metabolism; Mitogen-Activated Protein Kinase 3; Nerve Growth Factors/pharmacology; Neurotrophin 3; Phospholipase C gamma; Receptor Protein-Tyrosine Kinases/*metabolism; Serotonin/metabolism; Tretinoin/pharmacology; Ciliary Neurotrophic Factor; Receptors; Receptor; Tumor Cells; Cultured/chemistry/cytology/enzymology; Nerve Growth Factor/*metabolism; trkC
Monoamine-activated alpha2-macroglobulin (alpha2M) was shown to reduce the dopamine concentration in corpus striatum of adult rat brains and inhibit other neuronal functions in vivo and in vitro. As brain-derived neurotrophic factor, neurotrophin-4, and neurotrophin-3 are important neurotrophic factors for dopaminergic neurons, the effect of monoamine-activated alpha2M on signal transduction by trkB and trkC was investigated. The results show that monoamine-activated alpha2M binds to trkB and inhibits brain-derived neurotrophic factor/neurotrophin-4-promoted autophosphorylation of trkB in a dose-dependent manner in both trkB-expressing NIH3T3 (NIH3T3-trkB) and human neuroblastoma
Hu Y Q; Koo P H
Journal of neurochemistry
1998
1998-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Alteration of dopamine release by rat caudate putamen tissues superfused with alpha 2-macroglobulin.
alpha-Macroglobulins/drug effects/*pharmacology/physiology; Alzheimer Disease/metabolism; Animals; Caudate Nucleus/*drug effects/metabolism; Chemical; Dopamine/*metabolism; Male; Methylamines/pharmacology; Nerve Growth Factor/physiology; Nerve Growth Factors/physiology; Neurotoxins/*pharmacology; Parkinson Disease/metabolism; Perfusion; Putamen/*drug effects/metabolism; Rats; Receptors; Sprague-Dawley; Stimulation
Monoamine-activated alpha-2-macroglobulin (alpha 2M) has been shown to decrease the dopamine concentrations in rat caudate putamen (CP) in vivo as well as inhibit choline acetyltransferase activities in the culture of basal forebrain neurons. In this study, we further investigated the effects of methylamine-activated alpha 2M (MA-alpha 2M) upon striatal dopaminergic function by determining whether a direct infusion of this glycoprotein will alter dopamine (DA) release in vitro from superfused CP tissue fragments. In experiment 1, an infusion of 2.8 microM MA-alpha 2M produced a statistically significant increase in DA release compared with control superfusions. In experiment 2, varying doses (0, 0.7, 1.4, 2.8, 4.1 microM) of MA-alpha 2M were tested for their capacity to alter DA release. Only the 2.8 microM dose of MA-alpha 2M was effective in producing a significant increase of DA release. In experiment 3, the normal form of alpha 2M (N-alpha 2M) at 2.8 microM was compared with the control superfusions. The infusion of N-alpha 2M produced an increase in DA release which was substantially lower than the DA increase induced by MA-alpha 2M, and not significantly different from that of the control superfusion. These results show that MA-alpha 2M, like some other neurotoxins, can markedly alter CP dopaminergic function as indicated by the acute increase in DA release following infusion of this glycoprotein, and these effects are exerted at a relatively narrow range of doses. Taken together, these data suggest that this glycoprotein, if allowed to accumulate in the central nervous system (CNS), may promote some neurodegenerative changes that can occur in disorders like Parkinson's disease.
Hu Y Q; Liu B J; Dluzen D E; Koo P H
Journal of neuroscience research
1996
1996-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/jnr.490430109" target="_blank" rel="noreferrer noopener">10.1002/jnr.490430109</a>
Intracranial infusion of monoamine-activated alpha 2-macroglobulin decreases dopamine concentrations within the rat caudate putamen.
*Nerve Degeneration; alpha-Macroglobulins/*pharmacology/physiology/toxicity; Animals; Caudate Nucleus/*drug effects/metabolism; Dopamine/*metabolism; Infusion Pumps; Male; Putamen/*drug effects/metabolism; Rats; Sprague-Dawley
Monoamine-activated alpha 2-macroglobulin (alpha 2M) has been shown to inhibit choline acetyltransferase in basal forebrain neurons as well as neurotrophin-dependent neuronal functions. The objective of this study was to determine whether monoamine-activated alpha 2M can affect the caudate putamen (CP) dopaminergic system in vivo. Male rats received intracranial infusions of methylamine-activated alpha 2M (0.6 nmole) and contralateral infusions of its vehicle, phosphate-buffered saline (PBS). Five days following infusion, the animals were killed, the CP dissected into three rostral-caudal segments, and assayed for dopamine (DA) using a high-performance liquid chromatography system. Within the two rostral CP segments (the approximate site of cannula placement), statistically significant (26%) reductions of DA concentrations were obtained on the alpha 2M-infused side of the CP with 90-100% of the animals showing decreases. At a more distal (caudal) site of the CP, DA concentrations showed only an insignificant (12%) reduction. No differences in DA concentrations between sides infused with bovine serum albumin versus PBS or from olfactory tubercle samples were obtained in these animals. These results demonstrate that monoamine-activated alpha 2M is capable of producing significant degeneration of the nigrostriatal dopaminergic system in vivo and suggest that this factor may play a role in age-related neurodegenerative disorders such as Parkinson's disease.
Hu Y Q; Dluzen D E; Koo P H
Journal of neuroscience research
1994
1994-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/jnr.490380506" target="_blank" rel="noreferrer noopener">10.1002/jnr.490380506</a>
Inhibition of dopamine and choline acetyltransferase concentrations in rat CNS neurons by rat alpha 1- and alpha 2-macroglobulins.
alpha-Macroglobulins/administration & dosage/*pharmacology; Animals; Cells; Choline O-Acetyltransferase/*antagonists & inhibitors; Corpus Striatum/drug effects/*enzymology/metabolism; Cultured; Dopamine Antagonists/*pharmacology; Dopamine/analysis/*metabolism; Enzyme Activation/drug effects; Injections; Intraventricular; Male; Neurons/drug effects/*enzymology/metabolism; Rats; Serotonin/pharmacology; Sprague-Dawley; Stereotaxic Techniques
Previous studies have implicated human alpha-2-macroglobulin (alpha2M) as a potential regulator of neuronal development and function. Rat alpha-1-macroglobulin (alpha1M) and acute-phase alpha-2-macroglobulin (alpha2M) are murine homologues of human alpha2M. In this report, we tested the effect of intracranially infused serotonin-activated rat alpha1M (5HT-alpha1M) on the concentration of dopamine (DA) in the corpus striatum in vivo and the effect of
Hu Y Q; Liebl D J; Dluzen D E; Koo P H
Journal of neuroscience research
1998
1998-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/(SICI)1097-4547(19980215)51:4%3C541::AID-JNR14%3E3.0.CO;2-6" target="_blank" rel="noreferrer noopener">10.1002/(SICI)1097-4547(19980215)51:4%3C541::AID-JNR14%3E3.0.CO;2-6</a>