Upregulation of Bax protein and increased DNA degradation in ALS spinal cord motor neurons.
OBJECTIVE
To investigate if degeneration of motor neurons in amyotrophic lateral sclerosis (ALS) is related to altered levels of the apoptosis regulating proteins Bcl-2 and Bax. In addition, immunoreactivity of the cysteine protease ICH-IL and detection of motor neurons with DNA fragmentation, indicative of apoptosis, was also studied.


METHODS
The immunoreactivity of Bcl-2, Bax and ICH-1L were compared in ALS and control spinal cord motor neurons by immunohistochemical analysis and motor neurons with DNA fragmentation were identified by the TUNEL-method.


RESULTS
The results demonstrate an increased expression of Bax in the ALS material as compared to controls but no change in Bcl-2 and ICH-1L expressions. Moreover, a larger proportion of motor neurons stained positive for TUNEL in ALS spinal cords.


CONCLUSIONS
Present study suggest an upregulation of the cell death promoting protein Bax and increased DNA degradation, indicative of apoptosis, in spinal motor neurons of ALS patients.
Ekegren
T
T
Department of Neuroscience Neurology, University Hospital, Uppsala, Sweden.
Grundström
E
E
Lindholm
D
D
Aquilonius
S M
SM
D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000503:physiopathology; D017209:Apoptosis / Q000235:genetics; D004247:DNA / Q000378:metabolism*; D005260:Female; D019254:Genes, bcl-2 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D013127:Spinal Nerves / Q000473:pathology*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D004247:DNA