Abstract
Protease nexin-I (PN-1) is a 44 kDa serine proteinase inhibitor that rapidly inhibits thrombin by forming SDS stable complexes with serine at the catalytic site of the protease. Levels of both PN-1 and thrombin are increased in the brain in response to insults such as ischemia, suggesting roles in neural injury and repair processes. We now report that PN-1-protected cultured rat hippocampal neurons against glucose deprivation- induced damage (GDID), and the protection was abolished by equimolar thrombin. PN-1 reduced resting intracellular free calcium levels ([Ca2+],) and attenuated the elevation of [Ca2+], normally associated with GDID. Thrombin reduced neuronal survival and caused a significant increase in [Ca2+],. Submaximally toxic levels of thrombin exacerbated GDID. Calcium responses to thrombin were attenuated in neurons contacting PN-1 immunoreactive astrocytes. These findings suggest that PN-1 and thrombin play important roles in modulating neuronal calcium responses, and vulnerability, to metabolic/excitotoxic insults.
Original language | English (US) |
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Pages (from-to) | 5840-5850 |
Number of pages | 11 |
Journal | Journal of Neuroscience |
Volume | 15 |
Issue number | 8 |
State | Published - Aug 1995 |
Externally published | Yes |
Keywords
- Astrocytes
- Calcium
- Excitotoxicity
- Fura-2
- Glutamate
- Hippocampus
- Immunocytochemistry
- Neuronal death
- Protease nexin-1
- Thrombin
ASJC Scopus subject areas
- General Neuroscience