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: Fradejas, Noelia (poster)

Poster board 520 - Mon 10/07, 16:00 - Hall Y
Session 132 - Ischemia I
Abstract A132.7, published in FENS Forum Abstracts, vol. 3, 2006.
Ref.: FENS Abstr., vol.3, A132.7, 2006

Author(s) Fradejas N., Pastor D. & Calvo S.

Addresse(s) Fac. Medi. CRIB UCLM, Albacete, Spain

Title Involvement of caspase 11 in ischemia-induced astrocyte apoptosis.

Text We have previously shown that astrocytes subjected to ischemia undergo apoptosis upon ER-stress response activation and CHOP upregulation. Although CHOP is a well known mediator of the apoptosis caused by ER-stress, its downstream effectors have not been found yet. To continue with that work we have examined the role that caspase 11 might play as a downstream effector in the apoptosis induced by CHOP. Caspases are a family of cysteine proteases involved in regulating cytokine maturation and apoptosis and participate in the brain ischemic injury. Caspase-11 plays a crucial role in both inflammation and apoptosis. It not only activates caspase-1, required for the maturation of inflammatory cytokines, but also activates caspase-3, leading to cellular apoptosis under pathological conditions.
We have used primary cultures of rat astrocytes and oxygen and glucose (OGD) deprivation as an in vitro model of ischemia. We show that OGD induces a very significant upregulation of caspase 11 mRNA, measured by real time quantitative PCR, which is followed by the increase of caspase 11 protein. Time course of caspasa 11 upregulation in response to OGD follows the induction of CHOP, suggesting that CHOP could be inducing the caspasa 11 upregulation. In agreement with this, we have found that astrocyte treatment with the ER-stressors thapsigargin or tunicamycin induces also the upregulation of caspasa 11 and so does the expression of CHOP by means of an adenoviral vector. The role of caspase 11 in the apoptosis induced by OGD and ER-stress was further analyzed by using specific caspase 11 inhibitors on astrocytes challenged with OGD or ER-stress inducers. Those inhibitors induced a significant protection in both cases, suggesting that OGD- and ER-stress-induced astrocyte apoptosis are mediated, at least in part, by the caspase 11 activation.
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)	Fradejas N., Pastor D. & Calvo S.
Addresse(s)	Fac. Medi. CRIB UCLM, Albacete, Spain
Title	Involvement of caspase 11 in ischemia-induced astrocyte apoptosis.
Text	We have previously shown that astrocytes subjected to ischemia undergo apoptosis upon ER-stress response activation and CHOP upregulation. Although CHOP is a well known mediator of the apoptosis caused by ER-stress, its downstream effectors have not been found yet. To continue with that work we have examined the role that caspase 11 might play as a downstream effector in the apoptosis induced by CHOP. Caspases are a family of cysteine proteases involved in regulating cytokine maturation and apoptosis and participate in the brain ischemic injury. Caspase-11 plays a crucial role in both inflammation and apoptosis. It not only activates caspase-1, required for the maturation of inflammatory cytokines, but also activates caspase-3, leading to cellular apoptosis under pathological conditions. We have used primary cultures of rat astrocytes and oxygen and glucose (OGD) deprivation as an in vitro model of ischemia. We show that OGD induces a very significant upregulation of caspase 11 mRNA, measured by real time quantitative PCR, which is followed by the increase of caspase 11 protein. Time course of caspasa 11 upregulation in response to OGD follows the induction of CHOP, suggesting that CHOP could be inducing the caspasa 11 upregulation. In agreement with this, we have found that astrocyte treatment with the ER-stressors thapsigargin or tunicamycin induces also the upregulation of caspasa 11 and so does the expression of CHOP by means of an adenoviral vector. The role of caspase 11 in the apoptosis induced by OGD and ER-stress was further analyzed by using specific caspase 11 inhibitors on astrocytes challenged with OGD or ER-stress inducers. Those inhibitors induced a significant protection in both cases, suggesting that OGD- and ER-stress-induced astrocyte apoptosis are mediated, at least in part, by the caspase 11 activation. 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