Reduction in mitochondrial membrane peroxidizability index…
627
level of CEL and CML
,
was increased in the heart after atenolol treatment. These
results are in agreement with previous experiments in mice where increases in
CEL and CML were also observed (38). Several studies have reported dissociation
between markers of lipoxidation and those of glycoxidation or pure oxidation.
Thus, increasing fatty acid unsaturation in the rat heart by dietary manipulation
strongly elevated MDAL, whereas CML (which can be formed by lipoxidation and
glycoxidation) was only slightly elevated (52). On the other hand, MDAL negatively
correlated with longevity in the heart of mammals (26), but no correlation
between longevity and heart CML or CEL levels was observed in the same
investigation. Our results do not clarify why CML and CEL were increased. The
formation of those protein adducts could involve chemical reaction with oxidized
fragments coming from carbohydrates like glucose, but they may also be formed at
a high rate from glycolytic intermediates (40). It is possible that the atenolol
treatment increased the concentration of glycolytic intermediates, and that could
explain why the glycoxidation markers were increased in our experiment.
Polyunsaturated fatty acids are generally synthesized by modification of
saturated fatty acid precursors that are products of fatty acid synthase. This
process is catalized by two kind of specific enzymes: desaturases and elongases.
The enzymatic steps of microsomal fatty acid elongation involve the addition of
two-‐carbon units to a fatty acyl-‐CoA employing malonyl-‐CoA as the donor and
NADPH as the reducing agent. To date, seven ELOVL proteins (elongase enzymes
referred to as Elongation of very-‐long-‐chain fatty acids) have been identified, with
ELOVL1, 3, 6 and 7 preferring saturated and monounsaturated fatty acids as
substrate and ELOVL2, 4 and 5 being selective for polyunsaturated fatty acids
(PUFAs). All ELOVL proteins contain several stretches of amino acids that are fully
conserved in mice, rats and humans (53). The desaturase enzymes, which are also
highly conserved, insert double bonds at specific carbon atoms (the Δ number
indicates the position at which the double bond is introduced) in the fatty acid
chain and the fatty acid elongation system elongates the precursors in two-‐carbon
increments (54). The fatty acid desaturation pathway and the deacylation-‐
reacylation cycle are the main mechanisms responsible for the fatty acid
composition of cell membranes.
In the present investigation we estimated the desaturase and elongase
activities. The Δ5 (n-‐6) activity was lower in the atenolol group , as it has also been
reported in long-‐lived species, which show several fold lower Δ5 and Δ6
desaturase activities than short-‐lived ones (16,55). This can explain why 22:6n-‐3
and 20:4n-‐6 decrease, and 18:2n-‐6 and 18:3n-‐3 increase from short to long-‐lived
animals, since desaturases are the rate-‐limiting enzymes of the n-‐3 and n-‐6
pathways synthesizing the highly unsaturated PUFAs 20:4n-‐6 and 22:6n-‐3 from
their dietary precursors, 18:2n-‐6 and 18:3n-‐3, respectively. In our study the global
