Spinal cord trauma activates processing of xbp1 mRNA indicative of endoplasmic reticulum dysfunction.
The contribution of the various subcellular compartments in the induction of cell injury triggered by spinal cord trauma has not been clearly elucidated yet. In the present study, we investigated changes in mRNA levels of processed xbp1, ho-1, and hsp70 induced in mice by hemisection or contusion of the spinal cord. The expression of these genes is upregulated under conditions associated with endoplasmic reticulum (ER; xbp1, ho-1) dysfunction or impairment of cytoplasmic function (hsp70) respectively. When the functioning of the ER or the cytoplasm is impaired, unfolded proteins accumulate in these compartments. This is the warning signal for activation of the unfolded protein response (ER) and heat-shock response (cytoplasm) respectively. Spinal cord trauma activated the expression of these genes starting at 3 h and peaking at 6 h of recovery (processed xbp1, 12-fold and fivefold increase; ho-1, fourfold and eightfold increase; hsp70, fourfold, no increase, after contusion and hemisection, respectively). After 6 h of recovery, the rise in hsp70 mRNA levels was confined to the traumatized segment (fourfold), whereas a significant increase in processed xbp1 and ho-1 mRNA levels was also observed in the adjacent segments. This suggests a spread of the pathological process from the site of the primary impact into the surrounding tissue. After induction of spinal cord trauma processed xbp1 mRNA levels rose in a delayed fashion. This implies that the pathological process that causes impairment of ER functioning, starts with a delay of a few hours after induction of trauma and may therefore be amenable to therapeutic intervention.
Aufenberg
Christoph
C
Laboratory of Molecular Neurobiology, Max Planck Institute for Neurological Research, Cologne, Germany.
Wenkel
Simone
S
Mautes
Angelika
A
Paschen
Wulf
W
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000473:pathology*; D015870:Gene Expression; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D000071701:Regulatory Factor X Transcription Factors; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1
D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; D051547:Heme Oxygenase-1