Transglutaminase 2 interaction with small heat shock proteins mediate cell survival upon excitotoxic stress

Daniela Caccamo, Salvatore Condello, Nadia Ferlazzo, Monica Currò, Martin Griffin, Riccardo Ientile*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Transglutaminase 2 has been postulated to be involved in the pathogenesis of central nervous system neurodegenerative disorders. However, its role in neuronal cell death remains to be elucidated. Excitotoxicity is a common event underlying neurodegeneration. We aimed to evaluate the protein targets for transglutaminase 2 in cell response to NMDA-induced excitotoxic stress, using SH-SY5Y neuroblastoma cells which express high tranglutaminase 2 levels upon retinoic acid-driven differentiation toward neurons. NMDA-evoked calcium increase led to transglutaminase 2 activation that mediated cell survival, as at first suggested by the exacerbation of NMDA toxicity in the presence of R283, a synthetic competitive inhibitor of transglutaminase active site. Assays of R283-mediated transglutaminase inhibition showed the involvement of enzyme activity in NMDA-induced reduction in protein basal levels of pro-apoptotic caspase-3 and the stress protein Hsp20. However, this occurred in a way different from protein cross-linking, given that macromolecular assemblies were not observed in our experimental conditions for both proteins. Co-immunoprecipitation experiments provided evidence for the interaction, in basal conditions, between transglutaminase 2 and Hsp20, as well as between Hsp20 and Hsp27, a major anti-apoptotic protein promoting caspase-3 inactivation and degradation. NMDA treatment disrupted both these interactions that were restored upon transglutaminase 2 inhibition with R283. These results suggest that transglutaminase 2 might be protective against NMDA-evoked excitotoxic insult in neuronal-like SH-SY5Y cells in a way, independent from transamidation that likely involves its interaction with the complex Hsp20/Hsp27 playing a pro-survival role. © 2011 Springer-Verlag.

Original languageEnglish
Pages (from-to)151-159
Number of pages9
JournalAmino Acids
Volume44
Issue number1
Early online date21 Sep 2011
DOIs
Publication statusPublished - Jan 2013

Fingerprint

Small Heat-Shock Proteins
N-Methylaspartate
Cell Survival
Cells
Transglutaminases
Caspase 3
Proteins
Enzyme inhibition
Apoptosis Regulatory Proteins
Central Nervous System Diseases
Enzyme activity
Neurology
Cell death
Heat-Shock Proteins
Tretinoin
Neuroblastoma
Immunoprecipitation
Neurodegenerative Diseases
Neurons
Toxicity

Keywords

  • excitotoxicity
  • neuronal-like SH-SY5Y cells
  • small heat shock proteins
  • transglutaminase 2
  • transglutaminase inhibitor R283

Cite this

Caccamo, Daniela ; Condello, Salvatore ; Ferlazzo, Nadia ; Currò, Monica ; Griffin, Martin ; Ientile, Riccardo. / Transglutaminase 2 interaction with small heat shock proteins mediate cell survival upon excitotoxic stress. In: Amino Acids. 2013 ; Vol. 44, No. 1. pp. 151-159.
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Transglutaminase 2 interaction with small heat shock proteins mediate cell survival upon excitotoxic stress. / Caccamo, Daniela; Condello, Salvatore; Ferlazzo, Nadia; Currò, Monica; Griffin, Martin; Ientile, Riccardo.

In: Amino Acids, Vol. 44, No. 1, 01.2013, p. 151-159.

Research output: Contribution to journalArticle

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