Melatonin prevents cytoskeletal alterations and oxidative stress induced by okadaic acid in N1E-115 cells

G. Benitez-King, I. Túnez, A. Bellon, G. G. Ortíz, F. Antón-Tay

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Progressive loss of neuronal cytoarchitecture is a major event that precedes neuronal death, both in neural aging and in neurodegenerative diseases. Cytoskeleton in neurodegenerative diseases is characterized by hyperphosphorylated tau assembled in neurofibrillary tangles. Tau protein promotes microtubule enlargement and its hyperphosphorylation inhibits tubulin assembly. Okadaic acid (OA) causes oxidative stress, tau hyperphosphorylation, and altered cytoskeletal organization similar to those observed in neurons of patients with dementia. Since melatonin acts by both enlarging microtubules and as a free-radical scavenger, in this work we studied the effects of melatonin on altered cytoskeletal organization induced by OA in N1E-115 neuroblastoma cells. Optic microscopy, morphometric analysis, and tubulin immunofluorescence staining of neuroblastoma cells incubated with 50 nM OA showed an intact microtubule network following the neurite profile similar to that observed in the vehicle-incubated cells when melatonin was added to the incubation media 2 h before OA. The melatonin effects on altered cytoskeletal organization induced by OA were dose-dependent and were not abolished by luzindole, the mt1 melatonin antagonist receptor. Also, increased lipid peroxidation and augmented apoptosis in N1E-115 cells incubated with 50 nM OA were prevented by melatonin. The results support the hypothesis that melatonin can be useful in the treatment of neurodegenerative diseases.

Original languageEnglish
Pages (from-to)151-159
Number of pages9
JournalExperimental Neurology
Volume182
Issue number1
DOIs
StatePublished - Jul 1 2003

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Okadaic Acid
Melatonin
Oxidative Stress
Microtubules
Neurodegenerative Diseases
Tubulin
Neuroblastoma
Melatonin Receptors
tau Proteins
Free Radical Scavengers
Neurofibrillary Tangles
Neurites
Cytoskeleton
Lipid Peroxidation
Fluorescent Antibody Technique
Dementia
Microscopy
Apoptosis
Staining and Labeling
Neurons

Keywords

  • Cytoskeleton
  • Melatonin
  • N1E-115 cells
  • Neurodegenerative diseases
  • Okadaic acid

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Melatonin prevents cytoskeletal alterations and oxidative stress induced by okadaic acid in N1E-115 cells. / Benitez-King, G.; Túnez, I.; Bellon, A.; Ortíz, G. G.; Antón-Tay, F.

In: Experimental Neurology, Vol. 182, No. 1, 01.07.2003, p. 151-159.

Research output: Contribution to journalArticle

Benitez-King, G. ; Túnez, I. ; Bellon, A. ; Ortíz, G. G. ; Antón-Tay, F. / Melatonin prevents cytoskeletal alterations and oxidative stress induced by okadaic acid in N1E-115 cells. In: Experimental Neurology. 2003 ; Vol. 182, No. 1. pp. 151-159.
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