INVESTIGADORES
ASTORT Francisco
congresos y reuniones científicas
Título:
LPS INDUCES HO-1 IN ADRENOCORTICAL CELLS
Autor/es:
FRANCISCO ASTORT; CAMILA MARTINEZ CALEJMAN; MARÍA MERCAU; ESTEBAN M. REPETTO; PABLO ARIAS; CORA B. CYMERYNG
Lugar:
Miami Beach, Florida
Reunión:
Congreso; HEME OXYGENASES IN BIOLOGY AND MEDICINE 6th INTERNATIONAL CONGRESS ON HEME OXYGENASES; 2009
Institución organizadora:
INTERNATIONAL CONGRESS ON HEME
Resumen:
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LPS INDUCES
HO-1 IN ADRENOCORTICAL CELLS
Francisco Astort; Camila Martinez Calejman; María Mercau; Esteban M.
Repetto; Pablo Arias; Cora B. Cymeryng.
Departments
of Physiology and Human Biochemistry. School of Medicine.
University of Buenos Aires. Buenos Aires. Argentina
Previous experiments from our
laboratory, demonstrating increases in HO-1 mRNA, protein, and activity levels
in the adrenal cortex of LPS-treated rats led us to hypothesize that HO-1
activity is involved in the modulation of steroid production stimulated by LPS.
As direct effects of LPS on adrenocortical cells have not been addressed, the
aim of the present study was to analyze the mechanism of HO-1 induction by LPS
in adrenocortical cells (Y1).
The expression of the LPS receptor
TLR-4 (RT-PCR) was detected in Y1 cells, its mRNA levels being unaffected by
LPS treatment (10 µg/ml for 24 h). HO-1 mRNA and protein (western blot) levels
were increased by LPS in a dose dependent way. HO-1 promoter activity was
studied with a luciferase reporter plasmid containing 4 kb from the murine
promoter of HO-1 [pGL2(-4)HO-1] and NFkB activity was evaluated using a
reporter plasmid containing an NFkB response element [pKb/LUC]. LPS-dependent
activation of pKb/LUC and pGL2(-4)HO-1 were prevented by co-incubation with the
IKK inhibitor, PS-1145. This inhibitor also blocked the LPS dependent increase
in steroid production in Y1 cells.
In summary, LPS-dependent HO-1
transcription in adrenocortical cells probably involves NFkB activation, as
PS-1145 prevented the activation of both HO-1 and Kb/LUC. Increased HO-1
activity may play two important roles: on the one hand, HO-1 could act as an
antioxidant enzyme protecting the cells from oxidative stress arising after LPS
stimulation; on the other, HO-1 activity could locally modulate
steroidogenesis.