TY - JOUR
T1 - Lysophosphatidic acid rescues RhoA activation and phosphoinositides levels in astrocytes exposed to ethanol
AU - Martínez, Susana E.
AU - Lázaro-Diéguez, Francisco
AU - Selva, Javier
AU - Calvo, Fernando
AU - Piqueras, Jaime Renau
AU - Crespo, Piero
AU - Claro, Enrique
AU - Egea, Gustavo
PY - 2007/8
Y1 - 2007/8
N2 - Long-term ethanol treatment substantially impairs glycosylation and membrane trafficking in primary cultures of rat astrocytes. Our previous studies indicated that these effects were attributable to a primary alteration in the dynamics and organization of the actin cytoskeleton, although the molecular mechanism(s) remains to be elucidated. As small Rho GTPases and phosphoinositides are involved in the actin cytoskeleton organization, we now explore the effects of chronic ethanol treatment on these pathways. We show that chronic ethanol treatment of rat astrocytes specifically reduced endogenous levels of active RhoA as a result of the increase of in the RhoGAP activity. Furthermore, ethanol-treated astrocytes showed reduced phosphoinositides levels. When lysophosphatidic acid was added to ethanol-treated astrocytes, it rapidly reverted actin cytoskeleton reorganization and raised active RhoA levels and phosphoinositides content to those observed in untreated astrocytes. Overall, our results indicate that the harmful effects of chronic exposure to ethanol on a variety of actin dynamics-associated cellular events are primarily because of alterations of activated RhoA and phosphoinositides pools.
AB - Long-term ethanol treatment substantially impairs glycosylation and membrane trafficking in primary cultures of rat astrocytes. Our previous studies indicated that these effects were attributable to a primary alteration in the dynamics and organization of the actin cytoskeleton, although the molecular mechanism(s) remains to be elucidated. As small Rho GTPases and phosphoinositides are involved in the actin cytoskeleton organization, we now explore the effects of chronic ethanol treatment on these pathways. We show that chronic ethanol treatment of rat astrocytes specifically reduced endogenous levels of active RhoA as a result of the increase of in the RhoGAP activity. Furthermore, ethanol-treated astrocytes showed reduced phosphoinositides levels. When lysophosphatidic acid was added to ethanol-treated astrocytes, it rapidly reverted actin cytoskeleton reorganization and raised active RhoA levels and phosphoinositides content to those observed in untreated astrocytes. Overall, our results indicate that the harmful effects of chronic exposure to ethanol on a variety of actin dynamics-associated cellular events are primarily because of alterations of activated RhoA and phosphoinositides pools.
KW - 5-bisphosphate
KW - Actin cytoskeleton
KW - Astrocytes
KW - Ethanol
KW - Fetal alcohol syndrome
KW - Lysophosphatidic acid
KW - Phosphatidylinositol 4
KW - RhoA
UR - http://www.scopus.com/inward/record.url?scp=34547436810&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34547436810&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2007.04581.x
DO - 10.1111/j.1471-4159.2007.04581.x
M3 - Article
C2 - 17442046
AN - SCOPUS:34547436810
SN - 0022-3042
VL - 102
SP - 1044
EP - 1052
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 4
ER -