Page 110 - 79_04

Alexia
Gómez
&
col.

It
is
known
that
the
low
DBI
observed
in
long-­-lived
species
is
due
to
changes

in
the
type
of
unsaturated
fatty
acids
in
the
membrane
composition.
There
is
a

systematic
redistribution
between
the
type
of
PUFAs
present
from
the
highly

unsaturated
docosahexaenoic
(22:6n-­-3)
and
sometimes
arachidonic
(20:4n-­-6)

acids
in
short-­-lived
species
to
the
less
unsaturated
linoleic
acid
(18:2n-­-6)
and,
in

some
cases,
linolenic
acid
(18:3n-­-3)
in
the
long-­-lived
ones
at
mitochondrial
and

tissue
levels
(16).
Among
these,
the
fatty
acid
contributing
most
to
decrease
the

global
fatty
acid
unsaturation
degree
in
long-­-lived
animals
is
22:6n-­-3.
With
the

purpose
of
checking
if
similar
changes
occur
in
our
model,
we
measured
the
full

fatty
acid
composition
of
heart
mitochondria
membranes.
We
found
that
atenolol

treatment
in
the
Wistar
rat
heart
leads
to
variations
in
several
fatty
acids,
but

among
them,
the
most
important,
quantitatively,
was
the
decrease
in
the
highly

unsaturated
22:6n-­-3,
which
was
responsible
to
a
great
extent
for
the
decrease
in

the
PI.
This
fatty
acid
is
present
in
tissue
cellular
membranes
at
lower
levels
in

long-­-lived
than
in
short-­-lived
animals,
including
the
long-­-lived
naked
mole-­-rats

(47)
and
it
also
decreases
after
atenolol
treatment
in
C57BL/6
mice
(38).
In
the

present
study,
moreover,
we
found
other
atenolol-­-induced
decreases
in
fatty
acids

which
were
involved
in
the
decrease
of
fatty
acid
unsaturation
(lower
PI):

decreases
in
20:4n-­-6,
22:4n-­-6,
22:5n-­-6,
22:5n-­-3
and
22:6n-­-3,
whereas
18:2n-­-6

increased.
It
is
also
interesting
that
in
the
senescence-­-accelerated
mouse
(SAM)

strain,
the
SAM-­-prone
mice
had
greater
levels
of
the
highly
polyunsaturated

peroxidation-­-prone
fatty
acids
22:6
n-­-3
and
20:4n-­-6
and
lower
levels
of
the
less

peroxidation-­-prone
18:2n-­-6
PUFA
in
their
membranes,
and
consequently
they
had

a
greater
PI
than
the
SAM-­-resistant
mice
(48,49).
SAM-­-prone
mice
also
showed

greater
degree
of
lipid
peroxides
in
their
tissues
than
SAM-­-resistant
mice
(50).

What
are
the
consequences
of
this
decrease
in
PI?
A
low
PI
(sensitivity
to

peroxidation)
and
DBI
(double
bound
index)
confer
higher
resistance
of

membranes
to
lipid
peroxidation
and
lower
lipoxidation-­-dependent
damage
to

macromolecules.
Previous
studies
have
shown
that
the
heart
of
long-­-lived
animals

has
lower
levels
of
MDAL,
a
specific
marker
of
lipoxidation-­-dependent
damage
to

proteins,
compared
to
short-­-lived
species
(26).
In
the
present
study
the
fatty
acid

unsaturation
decrease
(lower
PI)
after
atenolol
treatment
correlated
with
a

remarkable
decrease
in
MDAL
(49%
lower
in
the
atenolol
group).
Lipid

peroxidation
generates
products
like
MDAL
or
hydroxynonenal,
but
it
also

produces
secondary
free
radicals.
The
decreased
fatty
acid
unsaturation
degree
in

the
atenolol
group
could
thus
be
responsible
for
a
lower
lipid-­-derived
secondary

free
radical
formation,
decreased
specific
lipoxidation
markers
like
MDAL
and

damage
to
other
macromolecules
(51).

On
the
other
hand,
there
were
no
changes
in
the
protein
oxidation
markers

measured
(GSA
and
AASA),
but
in
contrast,
protein
glycoxidation,
quantified
as
the

626