Altered expression and posttranslational modification of neurofilaments in methylmalonic aciduria
Details
Serval ID
serval:BIB_CCFEB9716BEE
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Poster: Summary – with images – on one page of the results of a researche project. The summaries of the poster must be entered in "Abstract" and not "Poster".
Collection
Publications
Institution
Title
Altered expression and posttranslational modification of neurofilaments in methylmalonic aciduria
Title of the conference
ICIEM 2013, 12th International Congress of Inborn Errors of Metabolism
Address
Barcelona, Spain, September 3-6, 2013
ISBN
0141-8955
Publication state
Published
Issued date
2013
Volume
36
Series
Journal of Inherited Metabolic Diseases
Pages
S173
Language
english
Abstract
Neurofilaments (NF), the main components of axonal cytoskeleton, are known
to be involved in several neurodegenerative diseases. It has been reported that
methylmalonate and propionate affect phosphorylation of NFs. In an in vitro
model for methylmalonic aciduria our group has recently shown that 2-
methylcitrate (2-MCA) is the most toxic metabolite for developing brain cells.
Here, we studied the effects of repetitive administration of 1mM 2-
MCA every 12 hours over 3 days on the development of NFs in 3D
organotypic rat brain cell cultures.
By immunohistochemistry with antibodies specific for the different NF
subunits (light NFL, medium NFM, heavy NFH) as well as for phosphorylated
(p) and glycosylated (g) forms of NFs, we observed a
decrease of axonal labeling and a disorganized axonal pattern. Interestingly,
signal retention of p-NFM and g-NFM was observed in neuronal
soma. Western blotting showed the decrease of NFL and NFH
subunits.
Taken together, our data show that 2-MCA alters expression of the different
NF subunits as well as their post-translational modifications. This likely
results in disturbed NF assembly, abnormal accumulation of NF in neuronal
cell bodies and impairment of axonal development.We conclude thatNF are
involved in 2-MCA-induced neurodegeneration in methylmalonic aciduria.
to be involved in several neurodegenerative diseases. It has been reported that
methylmalonate and propionate affect phosphorylation of NFs. In an in vitro
model for methylmalonic aciduria our group has recently shown that 2-
methylcitrate (2-MCA) is the most toxic metabolite for developing brain cells.
Here, we studied the effects of repetitive administration of 1mM 2-
MCA every 12 hours over 3 days on the development of NFs in 3D
organotypic rat brain cell cultures.
By immunohistochemistry with antibodies specific for the different NF
subunits (light NFL, medium NFM, heavy NFH) as well as for phosphorylated
(p) and glycosylated (g) forms of NFs, we observed a
decrease of axonal labeling and a disorganized axonal pattern. Interestingly,
signal retention of p-NFM and g-NFM was observed in neuronal
soma. Western blotting showed the decrease of NFL and NFH
subunits.
Taken together, our data show that 2-MCA alters expression of the different
NF subunits as well as their post-translational modifications. This likely
results in disturbed NF assembly, abnormal accumulation of NF in neuronal
cell bodies and impairment of axonal development.We conclude thatNF are
involved in 2-MCA-induced neurodegeneration in methylmalonic aciduria.
Create date
14/02/2014 18:02
Last modification date
20/08/2019 15:47
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