Activation of retinoic acid signalling after sciatic nerve injury: up-regulation of cellular retinoid binding proteins.
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.
Zhelyaznik
Nina
N
Institut für Biologie II, RWTH Aachen, Kopernikusstr 16, 52074 Aachen, Germany.
Schrage
Kirsten
K
McCaffery
Peter
P
Mey
Jörg
J
D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D003124:Colorimetry / Q000295:instrumentation / Q000379:methods; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D007641:Keratolytic Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009409:Nerve Crush / Q000379:methods; D016900:Neurofilament Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D050697:Retinal Dehydrogenase; D000072516:Retinoic Acid 4-Hydroxylase; D047488:Retinoid X Receptors; D012177:Retinol-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D054840:Retinol-Binding Proteins, Cellular; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000295:instrumentation / Q000379:methods; D009418:S100 Proteins / Q000378:metabolism; D012584:Sciatic Nerve / Q000187:drug effects* / Q000293:injuries* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation
D007641:Keratolytic Agents; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; D009418:S100 Proteins; D014157:Transcription Factors; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase; D000445:Aldehyde Oxidoreductases; D050697:Retinal Dehydrogenase