INVESTIGADORES
MARTINEZ CALEJMAN Camila
artículos
Título:
Crosstalk between nitric oxide synthases and cyclooxygenase 2 in the adrenal cortex of rats under lipopolysaccharide treatment
Autor/es:
SANCHEZ, ROCÍO; MERCAU, MARÍA E.; REPETTO, ESTEBAN M.; MARTINEZ CALEJMAN, CAMILA; ASTORT, FRANCISCO; PEREZ, MATÍAS N.; ARIAS, PABLO; CYMERYNG, CORA B.
Revista:
Endocrine
Editorial:
Springer
Referencias:
Lugar: New York; Año: 2013 vol. 46 p. 659 - 667
ISSN:
1355-008X
Resumen:
The effect of lipopolysaccharide on the modulationof steroid production by adrenal cells has been recently acknowledged. The purpose of this study was to determine the in vivo effects of LPS on adrenal cyclooxygenase 2 (COX-2) expression, analyze its crosstalk with the nitric oxide synthase (NOS) system, and assess its involvementon the modulation of glucocorticoid production. Male Wistar rats were injected with LPS and with specificinhibitors for NOS and COX activities. PGE2 and corticosterone levels were determined by RIA. Protein levels were analyzed by immunoprecipitation and western blotting.Transfection assays were performed in murine adrenocortical Y1 cells. Results show that LPS treatment increases PGE2 production and COX-2 protein levels in the rat adrenalcortex. Systemic inhibition of COX-2 blunted the glucocorticoid response to ACTH, as well as the increase in NOS activity and the NOS-2 expression levels induced by LPS.Conversely, NOS inhibition prevented the LPS-dependent increase in PGE2 production, COX-2 protein levels, and the nitrotyrosine modification of COX-2 protein. Treatment ofadrenocortical cells with a NO-donor significantly potentiated the LPS-dependent increase in NFj B activity and COX-2 expression levels. In conclusion, our results show asignificant crosstalk between COX-2 and NOS in the adrenal cortex upon LPS stimulation, in which each activity has a positive impact on the other. In particular, as both theactivities differently affect adrenal steroid production, we hypothesize that this kind of fine modulation enables the gland to adjust steroidogenesis to prevent either an excessive or an insufficient response to the endotoxin challenge.
