کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4344581 | 1296667 | 2012 | 6 صفحه PDF | دانلود رایگان |
In the neurodegenerative disease amyotrophic lateral sclerosis (ALS), a number of proteins have been found to be hyperphosphorylated, including neurofilament proteins (NFs). In addition to protein phosphorylation, another important post-translational modification is O-glycosylation with β-N-acetylglucosamine residues (O-GlcNAc) and it has been found that O-GlcNAc can modify proteins competitively with protein phosphorylation, so that increased O-GlcNAc can reduce phosphorylation at specific sites. We evaluated a transgenic mouse model of ALS that overexpresses mutant superoxide dismutase (mSOD) and found that O-GlcNAc immunoreactivity levels are decreased in spinal cord tissue from mSOD mice, compared to controls. This reduction in O-GlcNAc levels is prominent in the motor neurons of spinal cord. We find that inhibition of O-GlcNAcase (OGA), the enzyme catalyzing removal of O-GlcNAc, using the inhibitor NButGT for 3 days, resulted in increased O-GlcNAc levels in spinal cord, both in mSOD and control mice. Furthermore, NButGT increased levels of O-GlcNAc modified NF-medium in spinal cords of control mice, but not in mSOD mice. These observations suggest that the neurodegeneration found in mSOD mice is associated with a reduction of O-GlcNAc levels in neurons, including motor neurons.
► We describe the distribution of O-GlcNAc modified proteins in mSOD mice.
► We examine changes in the levels of O-GlcNAc modified proteins using OGA inhibitor.
► Reductions in O-GlcNAc are prominent in the motor neurons in spinal cords of mSOD.
► Using inhibitor NButGT results in increased O-GlcNAc levels in mSOD and controls.
► The neurodegeneration in mSOD mice is associated with reductions of O-GlcNAc levels.
Journal: Neuroscience Letters - Volume 516, Issue 2, 16 May 2012, Pages 296–301