Hypoxia-mediated induction of heme oxygenase type I and carbon monoxide release from astrocytes protects nearby cerebral neurons from hypoxia-mediated apoptosis.
Antioxid Redox Signal
; 9(5): 543-52, 2007 May.
Article
em En
| MEDLINE
| ID: mdl-17330989
ABSTRACT
To study a putative paracellular protective mechanism of astrocytes for neurons, immunohistochemical analysis was performed in ischemic rat brain, which colocalized with the expression of heme oxygase-1 (HO- 1) in astroglias surrounding dying TUNEL-positive neurons. As an in vitro paradigm for ischemia, cultured astrocytes were exposed to normobaric hypoxia (pO(2) asymptotically equal to 10 torr), which triggered marked increase in the expression of a 33 kDa stress protein, identified as HO-1. Induction of HO-1 message was observed within 4 h of hypoxia and peaked at 12 h, accompanied by an accelerated transcription of HO-1 message. Consistent with the induction of HO-1, a platelet bioassay revealed production of carbon monoxide by reoxygenated astrocytes. The presence of CO in the medium decelerated the hypoxia-mediated apoptotic type of cell death in cultured cerebral neurons via lowering the activity of caspase-3, a key enzyme regulating apoptotic cell death. This protection against apoptosis was likely mediated by CO-mediated increases in intracellular cGMP, because exposure of hypoxic neurons to CO increased intracellular cGMP levels, and addition of cGMP analogue to hypoxic neuronal cultures suppressed caspase-3 activity and promoted neuronal survival. These data describe a potentially important paracellular pathway through which astrocytes may rescue nearby neurons from ischemic death.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Monóxido de Carbono
/
Hipóxia Celular
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Isquemia Encefálica
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Astrócitos
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Heme Oxigenase-1
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Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article