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Cyanide-stimulated inositol 1,4,5-trisphosphate formation: an intracellular neurotoxic signaling cascade.
- Source :
-
Journal of biochemical toxicology [J Biochem Toxicol] 1996; Vol. 11 (5), pp. 251-6. - Publication Year :
- 1996
-
Abstract
- Cyanide-induced neurotoxicity is associated with altered cellular Ca2+ homeostasis resulting in sustained elevation of cytosolic Ca2+. In order to characterize the effect of cyanide on intracellular signaling mechanisms, the interaction of KCN with the inositol 1,4,5-trisphosphate Ca2+ signaling system was determined in the PC12 cell line. KCN in the concentration range of 1.0-100 microM produced a rapid rise in intracellular IP3 levels (peak level occurred within 60 sec); 10 microM KCN elevated intracellular levels of IP3 to 148% of control levels. This response was mediated by phospholipase C (PLC) since U73122, a specific PLC inhibitor, blocked the response. Removal of Ca2+ from the incubation medium and chelation of intracellular Ca2+ with BAPTA partially attenuate the cyanide-stimulated IP3 generation, showing that the response is partially Ca2+ dependent. Also, treatment of cells with nifedipine or LaCl3, Ca2+ channel blockers, partially blocked the generation of IP3. This study shows that cyanide in concentrations as low as 1 microM stimulates IP3 generation that may be mediated by receptor and nonreceptor IP3 production since they have differential dependence on Ca2+. It is proposed that this response is an early intracellular signaling action that can contribute to altered Ca2+ homeostasis characteristic of cyanide neurotoxicity.
- Subjects :
- Animals
Calcium metabolism
Cytosol metabolism
Egtazic Acid analogs & derivatives
Egtazic Acid pharmacology
PC12 Cells metabolism
Rats
Type C Phospholipases antagonists & inhibitors
Type C Phospholipases metabolism
Inositol 1,4,5-Trisphosphate biosynthesis
PC12 Cells drug effects
Poisons toxicity
Potassium Cyanide toxicity
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0887-2082
- Volume :
- 11
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of biochemical toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 9110247
- Full Text :
- https://doi.org/10.1002/(SICI)1522-7146(1996)11:5<251::AID-JBT6>3.0.CO;2-J