|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 273, Issue 15, 9070-9077, April 10, 1998
From the Molecular Neurobiology Laboratory, Departments of
Neurology and Biochemistry/Molecular Biology, Mayo Clinic and Mayo
Foundation, Rochester, Minnesota 55905
Recent studies demonstrate that cAMP levels are
tightly controlled during demyelination and remyelination in Schwann
cells as cAMP decreases to 8-10% of normal following both sciatic
nerve crush or permanent transection injury and only begins to increase in the crushed nerve after remyelination (Poduslo, J. F.,
Walikonis, R. S., Domec, M., Berg, C. T., and
Holtz-Heppelmann, C. J. (1995) J. Neurochem. 65, 149-159). To investigate the mechanisms responsible for this change in
cAMP levels, cAMP phosphodiesterase (PDE) and adenylyl cyclase
activities were determined before and after sciatic nerve injury. Basal
cAMP PDE activity in soluble endoneurial homogenates of normal nerve
was 34.9 ± 1.9 pmol/mg of protein/min
(
Activity of Cyclic AMP Phosphodiesterases and Adenylyl Cyclase in
Peripheral Nerve after Crush and Permanent Transection Injuries
± S.E.; n = 10). This activity
increased about 3-fold within 6 days following both injuries. Basal PDE
activity remained elevated in the transected nerve, but declined to 70 pmol/mg of protein/min in the crushed nerve at 21 and 35 days following
injury. Isozyme-specific inhibitors and stimulators were used to
identify the PDE families in the sciatic nerve. The low
Km cAMP-specific (PDE4) and the
Ca2+/calmodulin-stimulated (PDE1) families were found to
predominate in assays using endoneurial homogenates. The PDE4 inhibitor
rolipram also increased cAMP levels significantly after incubation of
endoneurial tissue with various isozyme-specific inhibitors, indicating
that PDE4 plays a major role in determining cAMP levels. PDE4 mRNA was localized by in situ hybridization to cells identified
as Schwann cells by colabeling of S100, a Schwann cell specific
protein. Adenylyl cyclase activity declined following injury, from 3.7 pmol/mg of protein/min in normal nerve to 0.70 pmol/mg/min by 7 days
following injury. Both decreased synthesis and increased degradation
contribute, therefore, to the reduced levels of cAMP following
peripheral nerve injury and are likely critical to the process of
Wallerian degeneration.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  B. D. Sachs, G. S. Baillie, J. R. McCall, M. A. Passino, C. Schachtrup, D. A. Wallace, A. J. Dunlop, K. F. MacKenzie, E. Klussmann, M. J. Lynch, et al. p75 neurotrophin receptor regulates tissue fibrosis through inhibition of plasminogen activation via a PDE4/cAMP/PKA pathway J. Cell Biol., July 30, 2007; 177(6): 1119 - 1132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Groyer, B. Eychenne, C. Girard, K. Rajkowski, M. Schumacher, and F. Cadepond Expression and Functional State of the Corticosteroid Receptors and 11{beta}-Hydroxysteroid Dehydrogenase Type 2 in Schwann Cells Endocrinology, September 1, 2006; 147(9): 4339 - 4350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Filipek, B. Jastrzebska, M. Nowotny, and J. Kuznicki CacyBP/SIP, a Calcyclin and Siah-1-interacting Protein, Binds EF-hand Proteins of the S100 Family J. Biol. Chem., August 2, 2002; 277(32): 28848 - 28852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Howe and K. D. McCarthy Retroviral Inhibition of cAMP-Dependent Protein Kinase Inhibits Myelination But Not Schwann Cell Mitosis Stimulated by Interaction with Neurons J. Neurosci., May 15, 2000; 20(10): 3513 - 3521. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |