Activation of retinoic acid signalling after sciatic nerve injury

up-regulation of cellular retinoid binding proteins

Nina Zhelyaznik, Kirsten Schrage, Peter McCaffery, Jörg Mey

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

In mammalian peripheral nerves a crush lesion causes interactions between injured neurons, Schwann cells and haematogenous macrophages that can lead to successful axonal regeneration. We suggest that the transcriptional activator retinoic acid (RA), takes part in gene regulation after peripheral nerve injury and that RA signalling is activated via the cellular retinoic acid binding protein (CRABP)-II and cellular retinol binding protein (CRBP)-I. With RT-PCR and immunoblotting all necessary components of the RA signalling pathway were detected in the sciatic nerve of adult rats. These are retinoic acid receptors, retinoid X receptors, the retinoic acid synthesizing enzymes RALDH-1, RALDH-2, and RALDH-3, in addition, the cellular retinoid binding proteins CRBP-I, CRABP-I and CRABP-II. Enzyme activity of RALDH-2 was detectable in the nerve, and using a transgenic reporter mouse we found local activation of RA responsive elements in the regenerating nerve. Sciatic nerve crush as well as transection resulted in a more than 10-fold up-regulation of CRBP-I, which is thought to facilitate the synthesis of RA. Both kinds of injury also caused a 15-fold increase in transcript and protein concentration of CRABP-II, a possible mediator of RA transfer to its nuclear receptors.
Original languageEnglish
Pages (from-to)1033-1040
Number of pages8
JournalEuropean Journal of Neuroscience
Volume18
Issue number5
DOIs
Publication statusPublished - 2003

Keywords

  • Aldehyde Oxidoreductases
  • Animals
  • Blotting, Western
  • Colorimetry
  • Cytochrome P-450 Enzyme System
  • Gene Expression Regulation
  • Immunohistochemistry
  • Keratolytic Agents
  • Male
  • Mice
  • Mice, Transgenic
  • Nerve Crush
  • Neurofilament Proteins
  • RNA, Messenger
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Retinoic Acid
  • Retina
  • Retinal Dehydrogenase
  • Retinoid X Receptors
  • Retinol-Binding Proteins
  • Retinol-Binding Proteins, Cellular
  • Reverse Transcriptase Polymerase Chain Reaction
  • S100 Proteins
  • Sciatic Nerve
  • Signal Transduction
  • Time Factors
  • Transcription Factors
  • Tretinoin
  • Up-Regulation

Cite this

Activation of retinoic acid signalling after sciatic nerve injury : up-regulation of cellular retinoid binding proteins. / Zhelyaznik, Nina; Schrage, Kirsten; McCaffery, Peter; Mey, Jörg.

In: European Journal of Neuroscience, Vol. 18, No. 5, 2003, p. 1033-1040.

Research output: Contribution to journalArticle

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abstract = "In mammalian peripheral nerves a crush lesion causes interactions between injured neurons, Schwann cells and haematogenous macrophages that can lead to successful axonal regeneration. We suggest that the transcriptional activator retinoic acid (RA), takes part in gene regulation after peripheral nerve injury and that RA signalling is activated via the cellular retinoic acid binding protein (CRABP)-II and cellular retinol binding protein (CRBP)-I. With RT-PCR and immunoblotting all necessary components of the RA signalling pathway were detected in the sciatic nerve of adult rats. These are retinoic acid receptors, retinoid X receptors, the retinoic acid synthesizing enzymes RALDH-1, RALDH-2, and RALDH-3, in addition, the cellular retinoid binding proteins CRBP-I, CRABP-I and CRABP-II. Enzyme activity of RALDH-2 was detectable in the nerve, and using a transgenic reporter mouse we found local activation of RA responsive elements in the regenerating nerve. Sciatic nerve crush as well as transection resulted in a more than 10-fold up-regulation of CRBP-I, which is thought to facilitate the synthesis of RA. Both kinds of injury also caused a 15-fold increase in transcript and protein concentration of CRABP-II, a possible mediator of RA transfer to its nuclear receptors.",
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T1 - Activation of retinoic acid signalling after sciatic nerve injury

T2 - up-regulation of cellular retinoid binding proteins

AU - Zhelyaznik, Nina

AU - Schrage, Kirsten

AU - McCaffery, Peter

AU - Mey, Jörg

PY - 2003

Y1 - 2003

N2 - In mammalian peripheral nerves a crush lesion causes interactions between injured neurons, Schwann cells and haematogenous macrophages that can lead to successful axonal regeneration. We suggest that the transcriptional activator retinoic acid (RA), takes part in gene regulation after peripheral nerve injury and that RA signalling is activated via the cellular retinoic acid binding protein (CRABP)-II and cellular retinol binding protein (CRBP)-I. With RT-PCR and immunoblotting all necessary components of the RA signalling pathway were detected in the sciatic nerve of adult rats. These are retinoic acid receptors, retinoid X receptors, the retinoic acid synthesizing enzymes RALDH-1, RALDH-2, and RALDH-3, in addition, the cellular retinoid binding proteins CRBP-I, CRABP-I and CRABP-II. Enzyme activity of RALDH-2 was detectable in the nerve, and using a transgenic reporter mouse we found local activation of RA responsive elements in the regenerating nerve. Sciatic nerve crush as well as transection resulted in a more than 10-fold up-regulation of CRBP-I, which is thought to facilitate the synthesis of RA. Both kinds of injury also caused a 15-fold increase in transcript and protein concentration of CRABP-II, a possible mediator of RA transfer to its nuclear receptors.

AB - In mammalian peripheral nerves a crush lesion causes interactions between injured neurons, Schwann cells and haematogenous macrophages that can lead to successful axonal regeneration. We suggest that the transcriptional activator retinoic acid (RA), takes part in gene regulation after peripheral nerve injury and that RA signalling is activated via the cellular retinoic acid binding protein (CRABP)-II and cellular retinol binding protein (CRBP)-I. With RT-PCR and immunoblotting all necessary components of the RA signalling pathway were detected in the sciatic nerve of adult rats. These are retinoic acid receptors, retinoid X receptors, the retinoic acid synthesizing enzymes RALDH-1, RALDH-2, and RALDH-3, in addition, the cellular retinoid binding proteins CRBP-I, CRABP-I and CRABP-II. Enzyme activity of RALDH-2 was detectable in the nerve, and using a transgenic reporter mouse we found local activation of RA responsive elements in the regenerating nerve. Sciatic nerve crush as well as transection resulted in a more than 10-fold up-regulation of CRBP-I, which is thought to facilitate the synthesis of RA. Both kinds of injury also caused a 15-fold increase in transcript and protein concentration of CRABP-II, a possible mediator of RA transfer to its nuclear receptors.

KW - Aldehyde Oxidoreductases

KW - Animals

KW - Blotting, Western

KW - Colorimetry

KW - Cytochrome P-450 Enzyme System

KW - Gene Expression Regulation

KW - Immunohistochemistry

KW - Keratolytic Agents

KW - Male

KW - Mice

KW - Mice, Transgenic

KW - Nerve Crush

KW - Neurofilament Proteins

KW - RNA, Messenger

KW - Rats

KW - Rats, Sprague-Dawley

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KW - Retina

KW - Retinal Dehydrogenase

KW - Retinoid X Receptors

KW - Retinol-Binding Proteins

KW - Retinol-Binding Proteins, Cellular

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - S100 Proteins

KW - Sciatic Nerve

KW - Signal Transduction

KW - Time Factors

KW - Transcription Factors

KW - Tretinoin

KW - Up-Regulation

U2 - 10.1046/j.1460-9568.2003.02834.x

DO - 10.1046/j.1460-9568.2003.02834.x

M3 - Article

VL - 18

SP - 1033

EP - 1040

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 5

ER -