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>
Inhibition of nerve growth factor-stimulated neurite outgrowth by methylamine-modified alpha 2-macroglobulin.
alpha-Macroglobulins/metabolism/*pharmacology; Animals; Cells; Chick Embryo; Cultured; Drug Interactions; Female; Ganglia; Humans; Male; Methylamines/*pharmacology; Mice; Nerve Growth Factors/antagonists & inhibitors/metabolism/*pharmacology; Neurites/drug effects/*physiology/ultrastructure; Neurons/cytology/physiology; Placenta; Pregnancy; Spinal/physiology; Submandibular Gland
alpha 2-Macroglobulin (alpha 2M) is a rather ubiquitous protein in extracellular spaces of mammals. It is an inhibitor of endopeptidases, can be modified by aliphatic amines, and combines with a number of hormones/cytokines such as beta-nerve growth factor (NGF) [Koo PH, Stach RW (1989): J Neurosci Res 22:247]. The objective of this study is to compare the NGF-binding properties of methylamine-modified human alpha 2M (MA-alpha 2M) versus normal alpha 2M and their effects on the biological activity of NGF and neurite extension by embryonic chicken dorsal root ganglia. As determined by gel filtration, polyacrylamide gel electrophoresis, and equilibrium binding studies, these two forms of alpha 2M are similar in their binding affinities, with MA-alpha 2M binding about twice as much NGF as normal alpha 2M. Both normal alpha 2M and
Koo P H; Liebl D J
Journal of neuroscience research
1992
1992-04
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.490310412" target="_blank" rel="noreferrer noopener">10.1002/jnr.490310412</a>
Monoamine-modified Alpha-2-macroglobulin Inhibits Neurite Out-growth Of Embryonic Sensory Neurons, Cerebral Cortical-neurons And Pheochromocytoma Pc12 Cells
Biochemistry & Molecular Biology; Cell Biology; Life Sciences & Biomedicine - Other; Topics
Koo P H; Liebl D J
Faseb Journal
1992
1992-02
Journal Article or Conference Abstract Publication
n/a
Serotonin-activated Alpha-2-macroglobulin (alpha-2m) And Alpha-1m Respectively Blocks And Stimulates Neurite Outgrowth Of Rat Embryonic Forebrain Neurons And Adult-rat Sciatic-nerve Regeneration
Biochemistry & Molecular Biology; Cell Biology
Koo P H; Liebl D J
Journal of Cellular Biochemistry
1995
1995-04
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).
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>
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
Effect Of Alpha-2-macroglobulin (alpha(2)m) Versus Alpha(1)m On Monoamine-neurotransmitter Systems, Axonal Growth And The Survival Of Cerebral Neurons
Biochemistry & Molecular Biology; Cell Biology; Life Sciences & Biomedicine - Other; Topics
Liebl D J; Hu Y O; Dluzen D E; Koo P H
Faseb Journal
1994
1994-04
Journal Article or Conference Abstract Publication
n/a
Serotonin-activated alpha 2-macroglobulin inhibits neurite outgrowth and survival of embryonic sensory and cerebral cortical neurons.
Afferent/drug effects/ultrastructure; alpha-Macroglobulins/metabolism/*pharmacology; Animals; Bovine/pharmacology; Cell Survival/drug effects; Cells; Chick Embryo; Cultured; Frontal Lobe/*cytology/embryology; Ganglia; Humans; Nerve Growth Factors/*antagonists & inhibitors/pharmacology; Neurites/drug effects/ultrastructure; Neurons; Neurons/*drug effects/ultrastructure; Protein Binding; Rats; Serotonin/metabolism/*pharmacology; Serum Albumin; Spinal/*cytology/embryology
Methylamine-modified alpha-2-macroglobulin (MA-alpha 2M) has been recently shown to inhibit the biological activity of beta-nerve growth factor (NGF) in promoting neurite outgrowth by embryonic dorsal root ganglia in culture (Koo PH, Liebl DJ, J Neurosci Res 31:678-692, 1992). The objectives of this study are to determine whether alpha 2M can also be modified by larger aromatic biogenic amines such as
Liebl D J; Koo P H
Journal of neuroscience research
1993
1993-06
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.490350207" target="_blank" rel="noreferrer noopener">10.1002/jnr.490350207</a>
Monoamine-activated alpha 2-macroglobulin inhibits choline acetyltransferase of embryonic basal forebrain neurons and reversal of the inhibition by NGF and BDNF but not NT-3.
alpha-Macroglobulins/antagonists & inhibitors/*pharmacology; Animals; Biogenic Monoamines/*pharmacology; Brain-Derived Neurotrophic Factor; Cells; Choline O-Acetyltransferase/*antagonists & inhibitors; Cultured; Humans; Nerve Growth Factors/*pharmacology; Nerve Tissue Proteins/pharmacology; Neurons/drug effects/*metabolism; Neurotrophin 3; Prosencephalon/*cytology; Rats
Monoamine-activated alpha 2-macroglobulin (alpha 2M) has recently been shown to inhibit the growth and survival of cholinergic neurons of the basal forebrain (Liebl and Koo: J Neurosci Res 35:170-182, 1993). The mechanism of this inhibitory effect is believed to involve the regulation of growth factor activities by alpha 2M. The objectives of this study are to determine whether monoamine-activated alpha 2M can inhibit choline acetyltransferase (ChAT) activity of cholinergic basal forebrain neurons, and whether some common neurotrophins in the CNS can reverse the inhibition. This study demonstrates that both methylamine-activated alpha 2M (MA-alpha 2M) and serotonin-activated alpha 2M (5HT-alpha 2M) can dose-dependently suppress the expression of normal basal levels of ChAT activity in embryonic rat basal forebrain cells in vitro, while normal alpha 2M has little or no effect. As little as 0.35 microM monoamine-activated alpha 2M can suppress the ChAT activity, whereas either nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF), but not neurotrophin-3 (NT-3), stimulates ChAT expression of these cells. The addition of either NGF or BDNF to the alpha 2M-suppressed cells can increase ChAT activity back to its normal levels, while NT-3 can not. These results demonstrate that (1) monoamine-activated alpha 2M is a potent non-cytotoxic inhibitor of the ChAT activity in cholinergic basal forebrain neurons, and (2) NGF and BDNF are capable of not only stimulating the ChAT activity but can also specifically reverse the alpha 2M inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
Liebl D J; Koo P H
Journal of neuroscience research
1994
1994-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/jnr.490380406" target="_blank" rel="noreferrer noopener">10.1002/jnr.490380406</a>
Comparative binding of neurotrophins (NT-3, CNTF and NGF) and various cytokines to alpha 2-macroglobulin.
alpha-Macroglobulins/isolation & purification/*metabolism; Animals; Ciliary Neurotrophic Factor; Cytokines/isolation & purification/*metabolism; Electrophoresis; Humans; Male; Mice; Nerve Growth Factors/isolation & purification/*metabolism; Nerve Tissue Proteins/isolation & purification/*metabolism; Polyacrylamide Gel; Protein Binding; Rats; Recombinant Proteins/isolation & purification/metabolism; Serotonin/metabolism; Submandibular Gland/metabolism
All the nine common cytokines in this study (including NT-3, IGF-1, CNTF and
Liebl D J; Koo P H
Biochemical and biophysical research communications
1993
1993-06
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/10.1006/bbrc.1993.1760" target="_blank" rel="noreferrer noopener">10.1006/bbrc.1993.1760</a>