IMIBIO-SL   20937
INSTITUTO MULTIDISCIPLINARIO DE INVESTIGACIONES BIOLOGICAS DE SAN LUIS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
CIRCADIAN PATTERNS OF RORa AND REV-ERB EXPRESSION ARE MODIFIED IN THE HIPPOCAMPUS OF VITAMIN A-DEFICIENT RATS
Autor/es:
GOLINI REBECA; NAVIGATORE FONZO, LORENA; RANDAZZO G; ANZULOVICH, ANA CECILIA
Lugar:
San Luis
Reunión:
Congreso; XXXII Reunión Anual de la Sociedad de Biologia de Cuyo; 2014
Institución organizadora:
Sociedad de Biologia de Cuyo
Resumen:
In mammals, the circadian clock mechanism involves two interlocking
transcriptional-translational feedback loops. BMAL1/CLOCK heterodimer activates
the expression of clock and clock-controlled genes while the PER-CRY complex
represses it. The REV-ERB/ROR orphan nuclear receptors regulate the Bmal1
circadian expression contributing to the robustness of the clock mechanism.
Some evidence points out retinoids as regulators of clock genes activity
through retinoid receptors (RARs and RXRs). Previously, we have demonstrated
vitamin A deficiency modifies daily rhythms of clock genes expression in the
hippocampus, under 12h light:12h dark conditions; however, to date, no study on
clock endogenous (free running) circadian rhythms in that cerebral area has
been found. Thus, our objectives were: first, to investigate whether RORa and
REV-ERB also displays a circadian expression pattern in the rat hippocampus and
second, to evaluate the effect of a vitamin A-depleted diet on those temporal
patterns. Twenty one-day old Holtzman rats received a diet containing 4000 IU
of vitamin A/Kg diet (Control group), or the same diet devoided of vitamin A
(Vitamin A-deficient, VAD, group), during 3 months. In order to study
endogenous circadian rhythms, rats were maintained under constant darkness
conditions along 10 days before the experiment.
RORa and REV-ERB mRNA levels were determined by RT-PCR and RARα, RXRß
and BMAL1 proteins by immunoblotting, in hippocampus samples isolated every 4 h
during a 24h period. Regulatory regions of RORa and REV-ERB genes were scanned
for clock- and retinoic acid-responsive sites. E-box, RXRE, RARE and RORE sites were found. RORa and REV-ERB expression displays an endogenously-generated circadian
rhythm in the rat hippocampus, which was modified in the VAD group; probably, as
a consequence of alterations in the circadian patterns of BMAL1 and/or retinoic
acid receptors proteins.