FENS Forum 2006

FENS Forum 2006 - Vienna

For lectures, symposia and workshops, time indicates the beginning of the session.
For posters, authors are expected to be in attendance at their posters at the time indicated.

First author: Pastor, Dolores (poster)

Poster board 536 - Mon 10/07, 16:00 - Hall Y
Session 132 - Ischemia I
Abstract A132.23, published in FENS Forum Abstracts, vol. 3, 2006.
Ref.: FENS Abstr., vol.3, A132.23, 2006

Author(s) Pastor D. (1), Fradejas N. (1), Pende M. (2) & Calvo S. (1)

Addresse(s) (1) Fac. Medi. CRIB UCLM, Albacete, Spain; (2) INSERM U584 U810, Paris, France

Title Astrocyte survival to ischemic damage depends on the mTOR-p70 S6K pathway integrity.

Text Transient global cerebral ischemia triggers suppression of the initiation step of protein synthesis, a process which is controlled by endoplasmic reticulum (ER) function. The striking correlation between neuronal vulnerability and down-regulation of translation suggests that this cellular process plays a crucial role in the cascade of pathogenetic events leading to ischemic cell death. We have previously shown that astrocytes subjected to experimental ischemia undergo apoptosis depending on the ER-stress response activation which is characterized by the upregulation of ER-chaperons and the transcription factor CHOP. In this study, we have analyzed the role that the ribosomal p70 S6 kinase, protein implicated in the initiation of translation, plays in the astrocyte survival in response to ischemia.
We have used primary cultures of mouse astrocytes and oxygen and glucose (OGD) deprivation as an in vitro model of ischemia. We show here that OGD induces a very significant downregulation of S6K1 and S6K2 mRNA, measured by real time quantitative PCR. The mRNA downregulation is followed by a pronounced decrease of both phosphorylated and total S6K protein. Interestingly, the astrocyte viability following OGD is deeply impaired in the presence of rapamycin which inactivates the mTOR, an S6K kinase, necessary for S6K activation. The effects of S6K on astrocytes viability in response to ischemia were further analyzed in astrocytes obtained from mice deficient for S6K1 and S6K2. S6K1(-/-) /S6K2(-/-) astrocytes show much more sensitivity to the ischemic injury than wild-type mouse-derived astrocytes. In summary, our data suggest that the p70 S6K functions are impaired during astrocyte ischemia and that the integrity of this pathway is necessary for astrocyte to survive to ischemic insults.
Supported, in part, by grants SAF2001-0760 from CICYT and PAI05-017 from JCCM to S. C. Dolores Pastor has a Fellowship from JCCM.

Theme Neurological and psychiatric conditions
Ischemia / Cellular and molecular mechanisms

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Author(s)	Pastor D. (1), Fradejas N. (1), Pende M. (2) & Calvo S. (1)
Addresse(s)	(1) Fac. Medi. CRIB UCLM, Albacete, Spain; (2) INSERM U584 U810, Paris, France
Title	Astrocyte survival to ischemic damage depends on the mTOR-p70 S6K pathway integrity.
Text	Transient global cerebral ischemia triggers suppression of the initiation step of protein synthesis, a process which is controlled by endoplasmic reticulum (ER) function. The striking correlation between neuronal vulnerability and down-regulation of translation suggests that this cellular process plays a crucial role in the cascade of pathogenetic events leading to ischemic cell death. We have previously shown that astrocytes subjected to experimental ischemia undergo apoptosis depending on the ER-stress response activation which is characterized by the upregulation of ER-chaperons and the transcription factor CHOP. In this study, we have analyzed the role that the ribosomal p70 S6 kinase, protein implicated in the initiation of translation, plays in the astrocyte survival in response to ischemia. We have used primary cultures of mouse astrocytes and oxygen and glucose (OGD) deprivation as an in vitro model of ischemia. We show here that OGD induces a very significant downregulation of S6K1 and S6K2 mRNA, measured by real time quantitative PCR. The mRNA downregulation is followed by a pronounced decrease of both phosphorylated and total S6K protein. Interestingly, the astrocyte viability following OGD is deeply impaired in the presence of rapamycin which inactivates the mTOR, an S6K kinase, necessary for S6K activation. The effects of S6K on astrocytes viability in response to ischemia were further analyzed in astrocytes obtained from mice deficient for S6K1 and S6K2. S6K1(-/-) /S6K2(-/-) astrocytes show much more sensitivity to the ischemic injury than wild-type mouse-derived astrocytes. In summary, our data suggest that the p70 S6K functions are impaired during astrocyte ischemia and that the integrity of this pathway is necessary for astrocyte to survive to ischemic insults. Supported, in part, by grants SAF2001-0760 from CICYT and PAI05-017 from JCCM to S. C. Dolores Pastor has a Fellowship from JCCM.
Theme	Neurological and psychiatric conditions Ischemia / Cellular and molecular mechanisms