Home LiteratureArticle Details
PMID: 9425004 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Assembly of proteins to postsynaptic densities after transient cerebral ischemia.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 18 ·No. 2 ·1998-01-15 ·Pages 625-33

Hu BR, Park M, Martone ME, Fischer WH, Ellisman MH, Zivin JA

Abstract

Transient ischemia leads to changes in synaptic efficacy and results in selective neuronal damage during the postischemic phase, although the mechanisms are not fully understood. The protein composition and ultrastructure of postsynaptic densities (PSDs) were studied by using a rat transient ischemic model. We found that a brief ischemic episode induced a marked accumulation in PSDs of the protein assembly ATPases, N-ethylmaleimide-sensitive fusion protein, and heat-shock cognate protein-70 as well as the BDNF receptor (trkB) and protein kinases, as determined by protein microsequencing. The changes in PSD composition were accompanied by a 2.5-fold increase in the yield of PSD protein relative to controls. Biochemical modification of PSDs correlated well with an increase in PSD thickness observed in vivo by electron microscopy. We conclude that a brief ischemic episode modifies the molecular composition and ultrastructure of synapses by assembly of proteins to the postsynaptic density, which may underlie observed changes in synaptic function and selective neuronal damage.

MeSH Terms
Adenosine Triphosphatases/metabolism Amino Acid Sequence Animals Calcium-Calmodulin-Dependent Protein Kinase Type 2 Calcium-Calmodulin-Dependent Protein Kinases/metabolism Carrier Proteins/metabolism HSC70 Heat-Shock Proteins HSP70 Heat-Shock Proteins Ischemic Attack, Transient/metabolism Male Molecular Sequence Data N-Ethylmaleimide-Sensitive Proteins Protein Kinase C/metabolism Rats Rats, Wistar Receptor Protein-Tyrosine Kinases/metabolism Receptor, Ciliary Neurotrophic Factor Receptors, Nerve Growth Factor/metabolism Synapses/metabolism,ultrastructure Synaptic Transmission/physiology Vesicular Transport Proteins
Chemicals
Carrier Proteins HSC70 Heat-Shock Proteins HSP70 Heat-Shock Proteins Hspa8 protein, rat Receptor, Ciliary Neurotrophic Factor Receptors, Nerve Growth Factor Vesicular Transport Proteins Receptor Protein-Tyrosine Kinases Protein Kinase C Calcium-Calmodulin-Dependent Protein Kinase Type 2 Calcium-Calmodulin-Dependent Protein Kinases Adenosine Triphosphatases N-Ethylmaleimide-Sensitive Proteins Nsf protein, rat
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Hu B R
Department of Neuroscience, National Center for Microscopy and Imaging Research at San Diego, University of California, San Diego, La Jolla, California 92093-0624, USA.
Park M
Martone M E
Fischer W H
Ellisman M H
Zivin J A
References (62)
62 references, click to expand
  1. Phosphorylation of AMPA-type glutamate receptors by calcium/calmodulin-dependent protein kinase II and protein kinase C in cultured hippocampal neurons.
    J Neurosci. 1994 Mar;14(3 Pt 1):1123-9 PMID: 7509863
  2. Ischemia-induced translocation of Ca2+/calmodulin-dependent protein kinase II: potential role in neuronal damage.
    J Neurochem. 1992 May;58(5):1743-53 PMID: 1313852
  3. Effects of cerebral ischemia on N-methyl-D-aspartate and dihydropyridine-sensitive calcium currents. An electrophysiological study in the rat hippocampus in situ.
    Stroke. 1996 Jan;27(1):127-33 PMID: 8553388
  4. Regulation of protein kinase C.
    Curr Opin Cell Biol. 1997 Apr;9(2):161-7 PMID: 9069266
  5. Persistent translocation of Ca2+/calmodulin-dependent protein kinase II to synaptic junctions in the vulnerable hippocampal CA1 region following transient ischemia.
    J Neurochem. 1995 Jan;64(1):277-84 PMID: 7798923
  6. The formation of Golgi stacks from vesiculated Golgi membranes requires two distinct fusion events.
    Cell. 1995 Sep 22;82(6):895-904 PMID: 7553850
  7. Felix Hoppe-Seyler Lecture 1996. Mechanisms of intracellular protein transport.
    Biol Chem. 1996 Jul-Aug;377(7-8):407-10 PMID: 8922273
  8. An NSF-like ATPase, p97, and NSF mediate cisternal regrowth from mitotic Golgi fragments.
    Cell. 1995 Sep 22;82(6):905-14 PMID: 7553851
  9. Global brain ischemia and reperfusion: Golgi apparatus ultrastructure in neurons selectively vulnerable to death.
    Acta Neuropathol. 1995;90(1):17-30 PMID: 7572075
  10. 70-kDa heat shock protein and c-fos gene expression after transient ischemia.
    Stroke. 1990 Nov;21(11 Suppl):III107-11 PMID: 2122554
  11. Postischemic alterations of spontaneous activities in rat hippocampal CA1 neurons.
    Brain Res. 1990 Oct 22;530(2):257-60 PMID: 2265357
  12. Arc, a growth factor and activity-regulated gene, encodes a novel cytoskeleton-associated protein that is enriched in neuronal dendrites.
    Neuron. 1995 Feb;14(2):433-45 PMID: 7857651
  13. Isolation and characterization of postsynaptic densities from various brain regions: enrichment of different types of postsynaptic densities.
    J Cell Biol. 1980 Sep;86(3):831-45 PMID: 7410481
  14. Enhanced calcium uptake by CA1 pyramidal cell dendrites in the postischemic phase despite subnormal evoked field potentials: excitatory amino acid receptor dependency and relationship to neuronal damage.
    J Cereb Blood Flow Metab. 1992 Sep;12(5):773-83 PMID: 1324252
  15. Anoxic LTP sheds light on the multiple facets of NMDA receptors.
    Trends Neurosci. 1994 Nov;17(11):497-503 PMID: 7531893
  16. Alterations of Ca2+/calmodulin-dependent protein kinase II and its messenger RNA in the rat hippocampus following normo- and hypothermic ischemia.
    Neuroscience. 1995 Oct;68(4):1003-16 PMID: 8544977
  17. Stress-induced inhibition of protein synthesis initiation: modulation of initiation factor 2 and guanine nucleotide exchange factor activities following transient cerebral ischemia in the rat.
    J Neurosci. 1993 May;13(5):1830-8 PMID: 8478677
  18. Brief bursts of high-frequency stimulation produce two types of structural change in rat hippocampus.
    J Neurophysiol. 1980 Aug;44(2):247-58 PMID: 7411185
  19. Cytochemistry of synapses: selective staining for electron microscopy.
    Science. 1966 Dec 23;154(3756):1575-7 PMID: 5924927
  20. Direct modulation of calmodulin targets by the neuronal calcium sensor NCS-1.
    Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9253-8 PMID: 8799187
  21. Evidence for silent synapses: implications for the expression of LTP.
    Neuron. 1995 Aug;15(2):427-34 PMID: 7646894
  22. Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus.
    Science. 1995 Mar 17;267(5204):1658-62 PMID: 7886457
  23. A protein assembly-disassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation, and fusion.
    Cell. 1993 Nov 5;75(3):409-18 PMID: 8221884
  24. The structure of postsynaptic densities isolated from dog cerebral cortex. I. Overall morphology and protein composition.
    J Cell Biol. 1977 Jul;74(1):181-203 PMID: 194906
  25. Delayed neuronal death in the rat hippocampus following transient forebrain ischemia.
    Acta Neuropathol. 1984;64(2):139-47 PMID: 6475501
  26. Temporal profile of neuronal damage in a model of transient forebrain ischemia.
    Ann Neurol. 1982 May;11(5):491-8 PMID: 7103425
  27. Changes in the activity of protein kinase C and the differential subcellular redistribution of its isozymes in the rat striatum during and following transient forebrain ischemia.
    J Neurochem. 1991 Apr;56(4):1227-35 PMID: 2002338
  28. Post-ischemic potentiation of Schaffer collateral/CA1 pyramidal cell responses of the rat hippocampus in vivo: involvement of N-methyl-D-aspartate receptors.
    Brain Res. 1993 May 14;611(1):155-9 PMID: 8518943
  29. The rat brain postsynaptic density fraction contains a homolog of the Drosophila discs-large tumor suppressor protein.
    Neuron. 1992 Nov;9(5):929-42 PMID: 1419001
  30. Models for studying long-term recovery following forebrain ischemia in the rat. 2. A 2-vessel occlusion model.
    Acta Neurol Scand. 1984 Jun;69(6):385-401 PMID: 6464670
  31. Disturbances of cerebral protein synthesis and ischemic cell death.
    Prog Brain Res. 1993;96:161-77 PMID: 8332739
  32. Differential expression of the immediate early genes c-fos, c-jun, junB, and NGFI-B in the rat brain following transient forebrain ischemia.
    J Cereb Blood Flow Metab. 1994 Mar;14(2):206-16 PMID: 8113317
  33. Protein kinase C is translocated to cell membranes during cerebral ischemia.
    Neurosci Lett. 1990 Nov 13;119(2):228-32 PMID: 2280899
  34. N-methyl-D-aspartate receptor-mediated, prolonged afterdischarges of CA1 pyramidal cells following transient cerebral ischemia in the rat hippocampus in vivo.
    Brain Res. 1994 Sep 19;657(1-2):325-9 PMID: 7529643
  35. Excitotoxicity and the NMDA receptor--still lethal after eight years.
    Trends Neurosci. 1995 Feb;18(2):57-8 PMID: 7537407
  36. Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function.
    Annu Rev Neurosci. 1994;17:341-71 PMID: 8210179
  37. Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice.
    Nature. 1995 Jun 1;375(6530):400-4 PMID: 7760933
  38. Biosynthesis and posttranslational modifications of protein kinase C in human breast cancer cells.
    J Biol Chem. 1989 Aug 15;264(23):13902-9 PMID: 2474538
  39. Is NSF a fusion protein?
    Trends Cell Biol. 1995 Sep;5(9):335-9 PMID: 14732068
  40. Tyrosine phosphorylation and activation of mitogen-activated protein kinase in the rat brain following transient cerebral ischemia.
    J Neurochem. 1994 Apr;62(4):1357-67 PMID: 7510779
  41. The major tyrosine-phosphorylated protein in the postsynaptic density fraction is N-methyl-D-aspartate receptor subunit 2B.
    Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3954-8 PMID: 7513428
  42. Time course of the translocation and inhibition of protein kinase C during complete cerebral ischemia in the rat.
    J Neurochem. 1993 Oct;61(4):1308-14 PMID: 8376989
  43. Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of modulation.
    Nature. 1992 Apr 9;356(6369):521-3 PMID: 1373227
  44. Immunolocalization of the receptor tyrosine kinase EphA4 in the adult rat central nervous system.
    Brain Res. 1997 Oct 17;771(2):238-50 PMID: 9401744
  45. Studies on RNA synthesis in two populations of nuclei from the mammalian cerebral cortex.
    J Neurochem. 1973 Jul;21(1):19-40 PMID: 4720895
  46. Fine structural and cytochemical analysis of the staining of synaptic junctions with phosphotungstic acid.
    J Ultrastruct Res. 1968 Mar;22(5):361-75 PMID: 4173151
  47. Neurophysiological changes of spiny neurons in rat neostriatum after transient forebrain ischemia: an in vivo intracellular recording and staining study.
    Neuroscience. 1995 Aug;67(4):823-36 PMID: 7545798
  48. The biochemistry of synaptic regulation in the central nervous system.
    Annu Rev Biochem. 1994;63:571-600 PMID: 7979248
  49. Rapid translocation of cytosolic Ca2+/calmodulin-dependent protein kinase II into postsynaptic density after decapitation.
    J Neurochem. 1994 Oct;63(4):1529-37 PMID: 7931307
  50. Delayed neuronal death in the gerbil hippocampus following ischemia.
    Brain Res. 1982 May 6;239(1):57-69 PMID: 7093691
  51. Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: implications for the maturation of synaptic physiology and long-term potentiation.
    J Neurosci. 1992 Jul;12(7):2685-705 PMID: 1613552
  52. Calcium: still center-stage in hypoxic-ischemic neuronal death.
    Trends Neurosci. 1995 Feb;18(2):58-60 PMID: 7537408
  53. Stimulatory effects of protein kinase C and calmodulin kinase II on N-methyl-D-aspartate receptor/channels in the postsynaptic density of rat brain.
    J Neurochem. 1993 Jul;61(1):100-9 PMID: 7685812
  54. Role of oxidants in ischemic brain damage.
    Stroke. 1996 Jun;27(6):1124-9 PMID: 8650725
  55. Sequential development of reversible and irreversible neuronal damage following cerebral ischemia.
    J Neuropathol Exp Neurol. 1984 Mar;43(2):141-53 PMID: 6707703
  56. Increased production of the TrkB protein tyrosine kinase receptor after brain insults.
    Neuron. 1993 Feb;10(2):151-64 PMID: 8439408
  57. Fine structural nature of delayed neuronal death following ischemia in the gerbil hippocampus.
    Acta Neuropathol. 1984;62(3):209-18 PMID: 6695555
  58. Differential transcription and translation of immediate early genes in the gerbil hippocampus after transient global ischemia.
    J Cereb Blood Flow Metab. 1993 Nov;13(6):914-24 PMID: 8408317
  59. Excitatory interactions between glutamate receptors and protein kinases.
    J Neurobiol. 1994 Mar;25(3):304-11 PMID: 7910847
  60. Historical overview. Calcium, ischemia, and death of brain cells.
    Ann N Y Acad Sci. 1988;522:638-61 PMID: 2454060
  61. In vivo intracellular demonstration of an ischemia-induced postsynaptic potential from CA1 pyramidal neurons in rat hippocampus.
    Neuroscience. 1996 Dec;75(3):665-9 PMID: 8951862
  62. Uncoating ATPase is a member of the 70 kilodalton family of stress proteins.
    Cell. 1986 Apr 11;45(1):3-13 PMID: 2937542
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1998-01-15
Pages
625-33
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6792532
Subset
IM
Grants
NINDS NIH HHS · NS28121 · United States
NINDS NIH HHS · NS36810-01 · United States
NCRR NIH HHS · RR04050 · United States
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2