Calpain inhibitors delay injury-induced apoptosis in adult mouse spinal cord motor neurons.
Here, we investigated the effect of calpain inhibitors on apoptosis in organotypic adult spinal cord slices from mice. An increase in calpain I immunoreactivity was found in the nuclei of motor neurons from slices cultured for 30 min. After 4 h, the immunopositive motor neurons exhibited apoptotic changes including nuclear and chromatin condensation. Eight hours after excision, most motor neurons showed nuclear apoptotic features. Two calpain inhibitors, leupeptin and calpain inhibitor XI, inhibited apoptosis in the motor neurons while the caspase inhibitor Z-VAD.fmk had no effect. Leupeptin, but not calpain inhibitor XI and Z-VAD.fmk, also inhibited nucleosomal DNA fragmentation. These results suggest the involvement of calpain I in the induction of apoptosis in motor neurons of adult spinal cord and that apoptosis can be triggered independent of caspase activation.
Momeni
Hamid R
HR
Department of Cell and Organism Biology, Lund University, Lund, Sweden. hamidreza.momeni@cob.lu.se
Kanje
Martin
M
D000367:Age Factors; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002154:Calpain / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology* / Q000627:therapeutic use; D007150:Immunohistochemistry; D007976:Leupeptins / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D009924:Organ Culture Techniques; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors
D015853:Cysteine Proteinase Inhibitors; D006023:Glycoproteins; D007976:Leupeptins; C039304:calpain inhibitors; D002154:Calpain; D020169:Caspases; C112682:Capn1 protein, mouse; C032854:leupeptin