Concanavalin A Induces Cortical Neuron Apoptosis by Causing ROS Accumulation and Tyrosine Kinase Activation

Soyong Jang, Taddesse Yayeh, Yea Hyun Leem, Eun Mi Park, Yoshihisa Ito, Seikwan Oh

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The lectin, concanavalin A (Con A), is the most extensively investigated member of the lectin family of plant proteins, but its effects on cortical neurons and astrocytes are poorly understood. In cultured cortical neurons and astrocytes, Con A exhibited dose-dependent neurotoxicity, but this was not observed in astrocytes. Similarly, in the cortical areas of rat brains, intracranial administration of Con A caused neuronal but no astrocyte damage. Methyl-α-d-mannopyranoside, a competitor of Con A, blocked Con A-induced cell death, whereas AMPA/KA receptor antagonists showed partial blocking effects. Furthermore, the mRNA levels of TNF-α, IL-1β, and IL-6 were elevated in astrocytes and cortical neurons treated with Con A. Intracellular reactive oxygen species (ROS) levels were increased in Con A-treated cortical neurons, and N-acetyl-cysteine (NAC, an antioxidant) and diphenyleneiodonium (DPI, a NADPH oxidase inhibitor) reduced intracellular ROS accumulation. Likewise, AG556 (a TNF-α inhibitor) and AG82 (a tyrosine kinase inhibitor) both reduced Con A-induced intracellular ROS accumulation. Furthermore, Con A-induced tyrosine phosphorylation was decreased by NAC and by AG556. Taken together, Con A-induced apoptosis in cortical neurons occurred as a sequel to Con A binding to neuronal glycoproteins and intracellular ROS accumulation. Interestingly, Con A-induced cellular damage was observed in cortical neurons but not in astrocytes or microglia.

Original languageEnglish
Pages (from-to)3504-3514
Number of pages11
JournalNeurochemical Research
Volume42
Issue number12
DOIs
StatePublished - 1 Dec 2017

Keywords

  • Concanavalin A
  • Intracellular ROS
  • Neuronal apoptosis
  • Tyrosine kinase

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