Preconditioning (PC) is a cell adaptive response to oxidative stress and, with regard to neurons, can be considered as a neuroprotective strategy. The aim of the present study was to verify how neuronal-like differentiated SH‐SY5Y cells adapt to a mild and transient H2O2 induced oxidative stress and, hence, whether may be considered as more sensitive cell model to study PC pathways. A first screening allowed to define H2O2 concentrations for PC (10μM‐50μM), applied before damage(100μM H2O2). Cell viability measured 24 hours after 100μM H2O2–induced damage was ameliorated by 24‐hour pre‐exposure to low‐concentration H2O2 (10μM‐30μM) with cell size as well restored. Markers for apoptosis (Bcl‐2 and Bad), inflammation (iNOS), and redox system (MnSOD) were also determined, showing that, in cells pre‐exposed to 10μMH2O2 and then submitted to 100μM H2O2, Bcl‐2 levels were higher, Bad and iNOS levels were lower than those observed in damaged cells, and MnSOD levels were unchanged. Such findings show that (1) neuronal‐ like differentiated SH‐SY5Y cells are a suitable model to investigate PC response and more sensitive to the effect of a mild and transient H2O2‐induced oxidative stress with respect to other neuronal cells; (2) 10μMH2O2–induced PC is mediated by apoptotic and inflammatory pathways, unlike antioxidant system; (3) such neuroprotective strategy and underlying signals proven in neuronal‐like differentiated SH‐SY5Y cells may contribute to understand in vivo PC mechanisms and to define a window for pharmacological intervention, namely, related to ischemic brain damage. Significance of the study Neuronal‐like differentiated SH‐SY5Y cells are a suitable model to investigate PC, an endogenous neuroprotective response to a mild and transient H2O2‐induced oxidative stress, elicited by 24‐hour exposure to very low H2O2 concentrations and mediated by both apoptotic and inflammatory pathways. This model reflects in vivo PC mechanisms occurring after brain trauma and provides novel information about pathways and time of protection useful for an appropriate pharmacological intervention.

Neuronal‐like differentiated SH‐SY5Y cells adaptation to a mildand transient H2O2‐induced oxidative stress

Akki R.
Co-primo
Methodology
;
Siracusa R.
Co-primo
Methodology
;
Morabito R.
Secondo
Conceptualization
;
Remigante A.
Investigation
;
Campolo M.
Investigation
;
La Spada G.
Visualization
;
Cuzzocrea S.
Penultimo
Visualization
;
Marino A.
Ultimo
Supervision
2018-01-01

Abstract

Preconditioning (PC) is a cell adaptive response to oxidative stress and, with regard to neurons, can be considered as a neuroprotective strategy. The aim of the present study was to verify how neuronal-like differentiated SH‐SY5Y cells adapt to a mild and transient H2O2 induced oxidative stress and, hence, whether may be considered as more sensitive cell model to study PC pathways. A first screening allowed to define H2O2 concentrations for PC (10μM‐50μM), applied before damage(100μM H2O2). Cell viability measured 24 hours after 100μM H2O2–induced damage was ameliorated by 24‐hour pre‐exposure to low‐concentration H2O2 (10μM‐30μM) with cell size as well restored. Markers for apoptosis (Bcl‐2 and Bad), inflammation (iNOS), and redox system (MnSOD) were also determined, showing that, in cells pre‐exposed to 10μMH2O2 and then submitted to 100μM H2O2, Bcl‐2 levels were higher, Bad and iNOS levels were lower than those observed in damaged cells, and MnSOD levels were unchanged. Such findings show that (1) neuronal‐ like differentiated SH‐SY5Y cells are a suitable model to investigate PC response and more sensitive to the effect of a mild and transient H2O2‐induced oxidative stress with respect to other neuronal cells; (2) 10μMH2O2–induced PC is mediated by apoptotic and inflammatory pathways, unlike antioxidant system; (3) such neuroprotective strategy and underlying signals proven in neuronal‐like differentiated SH‐SY5Y cells may contribute to understand in vivo PC mechanisms and to define a window for pharmacological intervention, namely, related to ischemic brain damage. Significance of the study Neuronal‐like differentiated SH‐SY5Y cells are a suitable model to investigate PC, an endogenous neuroprotective response to a mild and transient H2O2‐induced oxidative stress, elicited by 24‐hour exposure to very low H2O2 concentrations and mediated by both apoptotic and inflammatory pathways. This model reflects in vivo PC mechanisms occurring after brain trauma and provides novel information about pathways and time of protection useful for an appropriate pharmacological intervention.
2018
File in questo prodotto:
File Dimensione Formato  
3119545.pdf

solo utenti autorizzati

Tipologia: Versione Editoriale (PDF)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 548.11 kB
Formato Adobe PDF
548.11 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3119545
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 19
  • ???jsp.display-item.citation.isi??? 19
social impact