Protease nexin-1 and thrombin modulate neuronal Ca2+ homeostasis and sensitivity to glucose deprivation-induced injury

Virginia L. Smith-Swintosky, Stephen Zimmer, John W. Fenton, Mark P. Mattson

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)5840-5850
Number of pages11
JournalJournal of Neuroscience
Volume15
Issue number8
StatePublished - Aug 1995
Externally publishedYes

Fingerprint

Protease Nexins
Thrombin
Homeostasis
Glucose
Wounds and Injuries
Calcium
Serpin E2
Neurons
Serine Proteinase Inhibitors
Poisons
Astrocytes
Serine
Catalytic Domain
Peptide Hydrolases
Ischemia

Keywords

  • Astrocytes
  • Calcium
  • Excitotoxicity
  • Fura-2
  • Glutamate
  • Hippocampus
  • Immunocytochemistry
  • Neuronal death
  • Protease nexin-1
  • Thrombin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Smith-Swintosky, V. L., Zimmer, S., Fenton, J. W., & Mattson, M. P. (1995). Protease nexin-1 and thrombin modulate neuronal Ca2+ homeostasis and sensitivity to glucose deprivation-induced injury. Journal of Neuroscience, 15(8), 5840-5850.

Protease nexin-1 and thrombin modulate neuronal Ca2+ homeostasis and sensitivity to glucose deprivation-induced injury. / Smith-Swintosky, Virginia L.; Zimmer, Stephen; Fenton, John W.; Mattson, Mark P.

In: Journal of Neuroscience, Vol. 15, No. 8, 08.1995, p. 5840-5850.

Research output: Contribution to journalArticle

Smith-Swintosky, VL, Zimmer, S, Fenton, JW & Mattson, MP 1995, 'Protease nexin-1 and thrombin modulate neuronal Ca2+ homeostasis and sensitivity to glucose deprivation-induced injury', Journal of Neuroscience, vol. 15, no. 8, pp. 5840-5850.
Smith-Swintosky, Virginia L. ; Zimmer, Stephen ; Fenton, John W. ; Mattson, Mark P. / Protease nexin-1 and thrombin modulate neuronal Ca2+ homeostasis and sensitivity to glucose deprivation-induced injury. In: Journal of Neuroscience. 1995 ; Vol. 15, No. 8. pp. 5840-5850.
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