Potentiation of intracellular Ca2+ mobilization by hypoxia-induced NO generation in rat brain striatal slices and human astrocytoma U-373 MG cells and its involvement in tissue damage
| Autor: | Antonella, Meini, Alberto, Benocci, Maria, Frosini, Gian Pietro, Sgaragli, Julian Blanco, Garcia, Gian Paolo, Pessina, Carlo, Aldinucci, Mitri, Palmi |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
Nitroprusside Intracellular Space Astrocytoma In Vitro Techniques Nitric Oxide Ruthenium Cyclic N-Oxides Rats Sprague-Dawley Cell Line Tumor Animals Humans Drug Interactions Nitric Oxide Donors Enzyme Inhibitors Hypoxia Hydro-Lyases Dose-Response Relationship Drug Heparin Ryanodine Imidazoles Anticoagulants Free Radical Scavengers Corpus Striatum Rats Perfusion Drug Combinations NG-Nitroarginine Methyl Ester Calcium Fura-2 |
| Zdroj: | The European journal of neuroscience. 17(4) |
| ISSN: | 0953-816X |
| Popis: | The relationship between nitric oxide (NO) and intracellular Ca2+ in hypoxic-ischemic brain damage is not known in detail. Here we used rat striatal slices perfused under low-oxygen and Ca2+-free conditions and cultured human astrocytoma cells incubated under similar conditions as models to study the dynamics of intracellular NO and Ca2+ in hypoxia-induced tissue damage. Exposure of rat striatal slices for 70 min to low oxygen tension elicited a delayed and sustained increase in the release of 45Ca2+. This was potentiated by the NO donors sodium nitroprusside (SNP) and spermine-NO and inhibited by N-omega-nitro-L-arginine methyl ester (L-NAME) or by the NO scavenger 2-phenyl-4,4,5,5 tetramethylimidazoline-1-oxyl-3-oxide (PTIO). A membrane-permeant form of heparin in combination with either ruthenium red (RR) or ryanodine (RY) also inhibited 45Ca2+ release. In human astrocytoma U-373 MG cells, hypoxia increased intracellular Ca2+ concentration ([Ca2+]i) by 67.2 +/- 13.1% compared to normoxic controls and this effect was inhibited by L-NAME, PTIO or heparin plus RR. In striatal tissue, hypoxia increased NO production and LDH release and both effects were antagonized by L-NAME. Although heparin plus RR or RY antagonized hypoxia-induced increase in LDH release they failed to counteract increased NO production. These data therefore indicate that NO contributes to hypoxic damage through increased intracellular Ca2+ mobilization from endoplasmic reticulum and suggest that the NO-Ca2+ signalling might be a potential therapeutic target in hypoxia-induced neuronal degeneration. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text