CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
LPS induces Heme Oxygenase 1 in adrenocortical cells
Autor/es:
ASTORT, FRANCISCO; MARTINEZ CALEJMAN, CAMILA; MERCAU, MARÍA; REPETTO, ESTEBAN MARTÍN; ARIAS, PABLO; CYMERYNG, CORA BEATRIZ
Lugar:
Miami, Estados Unidos
Reunión:
Congreso; Heme Oxygenases in Biology and Medicine. 6th International Congress; 2009
Resumen:
<!--
/* Font Definitions */
@font-face
{font-family:Helvetica;
panose-1:2 11 6 4 2 2 2 2 2 4;
mso-font-charset:0;
mso-generic-font-family:swiss;
mso-font-pitch:variable;
mso-font-signature:536881799 -2147483648 8 0 511 0;}
@font-face
{font-family:"Cambria Math";
panose-1:2 4 5 3 5 4 6 3 2 4;
mso-font-charset:0;
mso-generic-font-family:roman;
mso-font-pitch:variable;
mso-font-signature:-1610611985 1107304683 0 0 159 0;}
@font-face
{font-family:Times;
panose-1:2 2 6 3 5 4 5 2 3 4;
mso-font-charset:0;
mso-generic-font-family:roman;
mso-font-pitch:variable;
mso-font-signature:536881799 -2147483648 8 0 511 0;}
/* Style Definitions */
p.MsoNormal, li.MsoNormal, div.MsoNormal
{mso-style-unhide:no;
mso-style-qformat:yes;
mso-style-parent:"";
margin:0cm;
margin-bottom:.0001pt;
mso-pagination:widow-orphan;
font-size:10.0pt;
font-family:"Times New Roman","serif";
mso-fareast-font-family:"Times New Roman";
mso-ansi-language:EN-US;
mso-fareast-language:EN-US;}
p.MsoBlockText, li.MsoBlockText, div.MsoBlockText
{mso-style-unhide:no;
margin-top:0cm;
margin-right:27.0pt;
margin-bottom:0cm;
margin-left:36.0pt;
margin-bottom:.0001pt;
text-align:center;
line-height:150%;
mso-pagination:widow-orphan;
font-size:12.0pt;
mso-bidi-font-size:10.0pt;
font-family:"Helvetica","sans-serif";
mso-fareast-font-family:"Times New Roman";
mso-bidi-font-family:"Times New Roman";
mso-ansi-language:EN-US;
mso-fareast-language:EN-US;}
.MsoChpDefault
{mso-style-type:export-only;
mso-default-props:yes;
font-size:10.0pt;
mso-ansi-font-size:10.0pt;
mso-bidi-font-size:10.0pt;}
@page Section1
{size:612.0pt 792.0pt;
margin:70.85pt 3.0cm 70.85pt 3.0cm;
mso-header-margin:36.0pt;
mso-footer-margin:36.0pt;
mso-paper-source:0;}
div.Section1
{page:Section1;}
-->
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.