Microarray analysis suggests the involvement of proteasomes, lysosomes, and matrix metalloproteinases in the response of motor neurons to root avulsion.
We used microarray analysis of RNA expression from punch samples from ventral horn of spinal cord to identify alterations in gene expression in motor neurons 3 days after proximal spinal root avulsion, a traumatic injury that results in the death of 80% of the motor neurons. This analysis identified the anticipated increases in expression of genes coding for proteins involved in the apoptosis cascades and abortive cell cycle re-entry, as well as decreases in expression of genes coding for proteins related to neuronal functional activity, including groups of genes related to energy metabolism, transporter proteins, ion channels, and receptors. It was also found that cathepsins, metalloproteinases, and proteasome-related protein products were highly up-regulated in motor neurons following axotomy. Each of these products represent pathways that have been implicated in other models of neuronal damage, but which have not previously been described as a response to axotomy.
Hu
Jian
J
Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Fink
David
D
Mata
Marina
M
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002403:Cathepsins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics; D007473:Ion Channels / Q000235:genetics; D008247:Lysosomes / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics*; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009097:Multienzyme Complexes / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012183:Retrograde Degeneration / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D019051:Rhizotomy / Q000009:adverse effects*; D013126:Spinal Nerve Roots / Q000293:injuries*
D018797:Cell Cycle Proteins; D007473:Ion Channels; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D020782:Matrix Metalloproteinases; D046988:Proteasome Endopeptidase Complex