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Upregulation of N-acetylaspartic acid alters inflammation, transcription and contractile associated protein levels in the stomach and smooth muscle contractility.
[canavan disease]
N-
acetylaspartic
acid
(
NAA
)
is
converted
into
aspartate
and
acetate
by
aspartoacylase
.
Abnormal
levels
of
the
enzyme
leads
to
accumulation
of
NAA
and
these
changes
have
been
observed
in
Canavan
disease
and
type
2
diabetes
.
How
upregulation
of
NAA
affect
the
gastrointestine
protein
levels
and
the
function
is
not
known
.
Incubation
of
rat
stomach
tissue
with
NAA
1
.
5
mM
,
1
.
5
microM
and
1
.
5
nM
induced
inflammatory
agents
TNFalpha
,
p
38
MAPK
,
iNOS
,
PKC
,
COX
2
and
ICAM
3
;
transcription
factors
phospho-
NF-kBp
65
,
cjun
and
cfos
;
contractile
proteins
MLCK
and
phospho
MLC
;
and
calcium
channel
alpha
1
C
and
calcium
channel
,
voltage-dependent
,
beta
3
subunit
compared
to
their
respective
control
.
Incubation
of
circular
smooth
muscle
cells
with
the
above
doses
of
NAA
induced
contractility
compared
to
the
control
.
These
studies
suggest
that
NAA
alters
proteins
levels
and
smooth
muscle
contractility
and
these
changes
likely
to
contribute
to
gastrointestinal
disorder
seen
in
these
diseases
.
