Page 112 - 79_04

Alexia
Gómez
&
col.

n-­-6
and
n-­-3
desaturases
were
also
significantly
lower
in
the
atenolol
treated

animals.
This
fact
can
explain
the
fatty
acid
unsaturation
decrease
in
the
atenolol

group.
Desaturation
pathways
would
make
available
in
situ
the
n-­-6
and
n-­-3
fatty

acids
to
phospholipid
acyltransferases
in
order
to
remodel
the
phospholipid
acyl

groups.
The
fact
that
acyltransferase/n-­-6
desaturase
activity
ratio
is
about
10:1
in

tissues
(56)
reinforces
the
idea
that
regulation
of
desaturases
can
be
the
main

limiting
factor
responsible
for
the
observed
fatty
acid
unsaturation-­-longevity

relationship
(40),
as
well
as
for
the
fatty
acid
changes
observed
in
the
present

study.
On
the
other
hand,
in
this
study
we
found
a
decrease
in
the
following

elongase
activities
in
the
atenolol
group:
ELOVL
1/3,
which
catalyzes
the
formation

of
saturated
fatty
acids
containing
as
many
as
26-­-carbons;
ELOVL
5
(n-­-6),
that

catalyzes
the
initial
and
rate-­-limiting
desaturation
of
C18:2n-­-6
and
C18:3n-­-3
for

the
production
of
longer-­-chain
PUFAs;
and
ELOVL
2/5
(n-­-6)
and
(n-­-3)
which
are

involved
in
PUFA
elongation
from
C20:3n-­-6
and
C20:4n-­-3.
The
lower
elongase

activities
in
atenolol
treated
animals
may
be
responsible
for
the
decrease
in
the

acyl
chain
length
in
this
group.

An
intact
respiratory
chain
is
needed
to
get
the
maximum
capacity
available

for
mitochondrial
energy
production.
Besides,
studies
in
rodents
show
that
the

amount
of
respiratory
complexes
in
the
respiratory
chain
can
change
in

experimental
modifications
that
extend
life-­-span.
Therefore,
we
measured
the

amounts
of
the
four
respiratory
complexes
in
our
study.
There
were
no
differences

in
the
amount
of
any
of
the
complexes
except
in
the
NDUFA9
complex
I
subunit,

which
was
lower
in
the
atenolol
group.
In
previous
studies
of
methionine

restriction
(57)
and
caloric
restriction
(58)
it
has
been
observed
that
the
amount

of
complex
I
was
decreased.
It
is
well
known
that
both
complex
I
and
complex
III

produce
ROS
in
isolated
mitochondria
(23,59).
However,
the
difference
in
ROS

production
between
species
with
different
longevities
and
between
caloric

restricted
and
ad
libitum-­-fed
animals
seems
to
come
exclusively
from
complex
I

(23).
Then,
the
slight
decrease
observed
in
the
complex
I
amount
in
our
study
can

be
responsible
for
the
non-­-significant
trend
to
decrease
mitochondrial
ROS

production
with
complex
I
linked
substrates
(glutamate/malate),
and
probably
the

adaptive
response
of
the
MnSOD
content.
This
decrease
would
not
be
as

remarkable
as
in
the
case
of
caloric
or
methionine
restriction,
in
which
the
time
of

treatment
was
longer
(7
weeks)
in
contrast
to
the
15
days
of
atenolol
treatment

implemented
here.

AIF
is
a
mitochondrial
flavoprotein
involved
in
the
assembly/manteinance

of
complex
I,
and
besides
its
role
in
apoptosis,
it
is
also
required
for
mitochondrial

oxidative
phosphorylation
(22).
Similarly
to
what
was
previously
reported
in

atenolol
treated
mice
(38),
in
the
present
investigation
AIF
did
not
change
after

atenolol
treatment,
suggesting
that
the
decrease
in
apoptosis
that
was
observed
in

628