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- Title
Aspirin provides cyclin-dependent kinase 5-dependent protection against subsequent hypoxia/reoxygenation damage in culture.
- Authors
Vartiainen, Nina; Keksa-Goldsteine, Velta; Goldsteins, Gundars; Koistinaho, Jari
- Abstract
Abstract Aspirin [acetylsalicylic acid (ASA)] is an anti-inflammatory drug that protects against cellular injury by inhibiting cyclooxygenases (COX), inducible nitric oxide synthase (iNOS) and p44/42 mitogen-activated protein kinase (p44/42 MAPK), or by preventing translocation of nuclear factor κB (NF-κB). We studied the effect of ASA pre-treatment on neuronal survival after hypoxia/reoxygenation damage in rat spinal cord (SC) cultures. In this injury model, COX, iNOS and NF-κB played no role in the early neuronal death. A 20-h treatment with 3 m m ASA prior to hypoxia/reoxygenation blocked the hypoxia/reoxygenation-induced lactate dehydrogenase (LDH) release from neurons. This neuroprotection was associated with increased phosphorylation of neurofilaments, which are substrates of p44/42 MAPK and cyclin-dependent kinase 5 (Cdk5). PD90859, a p44/42 MAPK inhibitor, had no effect on ASA-induced tolerance, but olomoucine and roscovitine, Cdk5 inhibitors, reduced ASA neuroprotection. Hypoxia/reoxygenation alone reduced both the protein amount and activity of Cdk5, and this reduction was inhibited by pre-treatment with ASA. Moreover, the protein amount of a neuronal Cdk5 activator, p35, recovered after reoxygenation only in ASA-treated samples. The prevention of the loss in Cdk5 activity during reoxygenation was crucial for ASA-induced protection, because co-administration of Cdk5 inhibitors at the onset ofreoxygenation abolished the protection. In conclusion, pre-treatment with ASA induces tolerance against hypoxia/reoxygenation damage in spinal cord cultures by restoring Cdk5 and p35 protein expression.
- Subjects
ASPIRIN; CYCLIN-dependent kinases; HYPOXEMIA
- Publication
Journal of Neurochemistry, 2002, Vol 82, Issue 2, p329
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1046/j.1471-4159.2002.00959.x