INVESTIGADORES
PODESTA Ernesto Jorge
artículos
Título:
Valproic acid alters mitochondrial colesterol transport in Y1 adrenocortical cells.
Autor/es:
BRION L, GOROSTIZAGA A, GÓMEZ NV, PODESTÁ EJ, CORNEJO MACIEL F, PAZ C
Revista:
TOXICOLOGY IN VITRO : AN INTERNATIONAL JOURNAL PUBLISHED IN ASSOCIATION WITH BIBRA.
Editorial:
PERGAMON-ELSEVIER SCIENCE LTD
Referencias:
Año: 2010 vol. 25 p. 7 - 12
ISSN:
0887-2333
Resumen:
Several reports suggest putative interactions between valproic acid (VPA) treatment and the hypothalamus
pituitaryadrenal axis. Given that VPA alters mitochondrial functions, an action of this drug on a
mitochondrial process such as steroid synthesis in adrenal cells should be expected. In order to disclose
a putative action of VPA on the adrenocortical cell itself we evaluated VPA effects on regulatory steps of
the acute stimulation of steroidogenesis in Y1 adrenocortical cells. This study demonstrates that VPA
increases progesterone production in non-stimulated cells without inducing the levels of SteroidogenicSteroidogenic
Acute Regulatory (StAR) protein, which facilitates cholesterol transport. This result suggests that VPA
increases mitochondrial cholesterol transport through a StAR-independent mechanism and is further
supported by the fact that in isolated mitochondria VPA stimulates exogenous cholesterol metabolization
to progesterone. VPA also reduces the cAMP-mediated increase of the StAR protein, mRNA levels, promoter
activity and progesterone production. In summary, the present data show that VPA can alter steroid
production in adrenal cells by a complex mechanism that mainly involves an action on cholesterol
access to the inner mitochondrial membrane. The VPA-mediated increase of basal steroidogenesis could
be linked to the increase of basal cortisolemia described in patients under VPA treatment.cute Regulatory (StAR) protein, which facilitates cholesterol transport. This result suggests that VPA
increases mitochondrial cholesterol transport through a StAR-independent mechanism and is further
supported by the fact that in isolated mitochondria VPA stimulates exogenous cholesterol metabolization
to progesterone. VPA also reduces the cAMP-mediated increase of the StAR protein, mRNA levels, promoter
activity and progesterone production. In summary, the present data show that VPA can alter steroid
production in adrenal cells by a complex mechanism that mainly involves an action on cholesterol
access to the inner mitochondrial membrane. The VPA-mediated increase of basal steroidogenesis could
be linked to the increase of basal cortisolemia described in patients under VPA treatment.