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)|
|Number of pages||11|
|Journal||Journal of Neuroscience|
|State||Published - Aug 1995|
- Neuronal death
- Protease nexin-1
ASJC Scopus subject areas