Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 77
Reciprocal neutralization of the antiapoptotic effects of magnetic fields and melatonin
due to interference between the two respective effectors, NO synthase and lipoxygenase
Silvia Nuccitelli, Flavia Radogna, Claudia Cerella, Milena De Nicola, Maria D’Alessio,
Andrea Magrini*, Antonio Bergamaschi*, Lina Ghibelli
Dipartimento di Biologia;*Cattedra di Medicina del Lavoro, Università di Roma Tor
Vergata, Via Ricerca Scientifica 1, 00133 Rome Italy. E-mail: silvia.nuccitelli@libero.it
Chemical/physical agents able to prevent apoptosis are receiving much attention for their
potential health hazard as tumor promoters and for their potential therapeutic role against
tissue degenerations. Magnetic fields (MFs), which have been shown to increase the
development of some tumors, reduce damage-induced apoptosis by a mechanism involving
Ca2+ entry into cells [Fanelli et al., FASEB J. 13, 95-102, 1999]. The neuro-hormone
melatonin, which is giving great expectations as therapeutic agent, also reduce damageinduced
apoptosis, again by a mechanism involving Ca2+ entry. The pathways responsible for
the two anti-apoptotic effects are complex and different (see accompanying presentations),
involving NO synthase (NOS) as one effector of MFs protection; and lipoxygenase (LOX) as
one of the effectors of melatonin protection. We wanted to know if the anti-apoptotic effects
of MFs and melatonin were synergic. Thus, we induced apoptosis in the presence of both
agents. Surprisingly we found that MFs and melatonin are not only not synergic, but abrogate
their respective anti-apoptotic effects. In order to verify whether this was due to an
interference between the effectors of the two different anti-apoptotic pathways, we inhibited
one or the other effectors (NOS with L-NAME and LOX with AA861) and checked whether
this would restore the protection mechanisms of melatonin or MFs, respectively. We found
that in U937 induced to apoptosis in the presence of both MFs and melatonin, L-NAME
abrogates MFs action and restores the anti-apoptotic effect of melatonin; vice versa, AA861
abrogates melatonin action and restores the anti-apoptotic effects of MFs. These results
indicate that the signal transduction pathways involving NOS and LOX interfere and
neutralise each other. The reciprocal interference implies that no direct inhibition is exerted
between the two enzymes, but rather the products of each interfere with the downstream
effectors of the other. No reports of effects of LOX or its products on NOS are available to
the best of our knowledge whereas. it is well known that NO inactivates lipoxygenase
[BBRC 219, 128-133, 1996]. These results recommend to explore the potential use of
melatonin as a mean to contrast the harmful effects of unwanted MFs exposure.
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