Increased calpain expression is associated with apoptosis in rat spinal cord injury: calpain inhibitor provides neuroprotection.
Calpain content was investigated in the lesion of rat spinal cord at 1, 4, 24, and 72 h following injury induced by the weight-drop (40 g-cm force) technique. Calpain content was increased in the lesion, and was highest at 24 h following injury. microCalpain mRNA level in the lesion was increased by 58.4% (p = 0.0135) at 24 h following trauma, compared to sham. Alterations in mRNA expression in the lesion increased bax/bcl-2 ratio by 20.8% (p = 0.0395) at this time point, indicating a commitment to apoptosis. Therapeutic effect of the calpain inhibitor E-64-d (1 mg/kg) was studied in SCI rats following administration for 24 h. Internucleosomal DNA fragmentation (apoptosis) was observed in SCI rats, but not in sham or E-64-d treated rats. These results indicate a new information that E-64-d has the therapeutic potential for inhibiting apoptosis in SCI.
Ray
S K
SK
Department of Neurology, Medical University of South Carolina, Charleston 29425, USA.
Matzelle
D D
DD
Wilford
G G
GG
Hogan
E L
EL
Banik
N L
NL
D000818:Animals; D017209:Apoptosis; D002154:Calpain / Q000037:antagonists & inhibitors / Q000235:genetics*; D015853:Cysteine Proteinase Inhibitors / Q000627:therapeutic use*; D053938:DNA Fragmentation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007930:Leucine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000201:enzymology* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology*; D014158:Transcription, Genetic; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D015853:Cysteine Proteinase Inhibitors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D002154:Calpain; D007930:Leucine; C108192:aloxistatin