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Protein kinase C and mouse sciatic nerve regeneration

Wiklund, Peter LU ; Ekström, Per A R LU ; Edbladh, Magnus LU ; Tonge, David and Edström, Anders LU (1996) In Brain Research 715(1-2). p.145-154
Abstract

We have studied the role of protein kinase C (PKC) in peripheral nerve regeneration by using the cultured adult mouse sciatic nerve, which displays regrowth of sensory axons under serum-free conditions. By the use of immunohistochemistry we show that one of the isoforms of PKC, PKCβ, is present in the nerve cell bodies of normal nerves and is upregulated after injury. In spite of this, the specific PKC inhibitor chelerythrine at 5 μM, a concentration well above its IC50 value for PKC, failed to reduce the outgrowth distance of new axons. This was not due to impermeability of the drug, since the same concentration caused a clear reduction of the injury-induced proliferation of Schwann cells in the crush region. Likewise,... (More)

We have studied the role of protein kinase C (PKC) in peripheral nerve regeneration by using the cultured adult mouse sciatic nerve, which displays regrowth of sensory axons under serum-free conditions. By the use of immunohistochemistry we show that one of the isoforms of PKC, PKCβ, is present in the nerve cell bodies of normal nerves and is upregulated after injury. In spite of this, the specific PKC inhibitor chelerythrine at 5 μM, a concentration well above its IC50 value for PKC, failed to reduce the outgrowth distance of new axons. This was not due to impermeability of the drug, since the same concentration caused a clear reduction of the injury-induced proliferation of Schwann cells in the crush region. Likewise, HA-1004, an inhibitor of cyclic nucleotide-dependent protein kinases, also lacked effect on outgrowth when used on its own, even at very high concentrations (100 μM). In contrast, outgrowth was significantly reduced when 5 μM chelerythrine and 5 μM HA-1004 were used in combination. In conclusion, the present results suggest that PKC-activity is important but not indispensable for the regeneration process. Successful completion of the latter could be achieved by several, perhaps redundant, phosphorylation systems.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
immunohistochemistry, inhibition, mouse, protein kinase C, regeneration, sciatic nerve
in
Brain Research
volume
715
issue
1-2
pages
145 - 154
publisher
Elsevier
external identifiers
  • scopus:0029885654
ISSN
0006-8993
DOI
10.1016/0006-8993(95)01570-1
language
English
LU publication?
yes
id
8a64d703-3339-4c36-b5e0-866c68a7fdaa
date added to LUP
2016-12-07 14:59:26
date last changed
2017-01-26 17:20:21
@article{8a64d703-3339-4c36-b5e0-866c68a7fdaa,
  abstract     = {<p>We have studied the role of protein kinase C (PKC) in peripheral nerve regeneration by using the cultured adult mouse sciatic nerve, which displays regrowth of sensory axons under serum-free conditions. By the use of immunohistochemistry we show that one of the isoforms of PKC, PKCβ, is present in the nerve cell bodies of normal nerves and is upregulated after injury. In spite of this, the specific PKC inhibitor chelerythrine at 5 μM, a concentration well above its IC<sub>50</sub> value for PKC, failed to reduce the outgrowth distance of new axons. This was not due to impermeability of the drug, since the same concentration caused a clear reduction of the injury-induced proliferation of Schwann cells in the crush region. Likewise, HA-1004, an inhibitor of cyclic nucleotide-dependent protein kinases, also lacked effect on outgrowth when used on its own, even at very high concentrations (100 μM). In contrast, outgrowth was significantly reduced when 5 μM chelerythrine and 5 μM HA-1004 were used in combination. In conclusion, the present results suggest that PKC-activity is important but not indispensable for the regeneration process. Successful completion of the latter could be achieved by several, perhaps redundant, phosphorylation systems.</p>},
  author       = {Wiklund, Peter and Ekström, Per A R and Edbladh, Magnus and Tonge, David and Edström, Anders},
  issn         = {0006-8993},
  keyword      = {immunohistochemistry,inhibition,mouse,protein kinase C,regeneration,sciatic nerve},
  language     = {eng},
  month        = {04},
  number       = {1-2},
  pages        = {145--154},
  publisher    = {Elsevier},
  series       = {Brain Research},
  title        = {Protein kinase C and mouse sciatic nerve regeneration},
  url          = {http://dx.doi.org/10.1016/0006-8993(95)01570-1},
  volume       = {715},
  year         = {1996},
}