Reactive oxygen species are related to ionic fluxes and volume decrease in apoptotic cerebellar granule neurons: Role of NOX enzymes

Berenice Hernández-Enríquez, Alicia Guemez-Gamboa, Julio Morán*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Reactive oxygen species (ROS) are produced early during apoptosis of cerebellar granule neurons induced by low potassium (K5) and staurosporine (Sts). In addition, K5 and Sts activate NADPH oxidases (NOX). Recently, we described that K5 and Sts induce apoptotic volume decrease (AVD) at a time when ROS generation and NOX activity occur. In the present study, we evaluated the relationship between ROS generation and ionic fluxes during AVD. Here, we showed that K5- and Sts-induced AVD was inhibited by antioxidants and that direct ROS production induced AVD. Moreover, NOX inhibitors eliminated AVD induced by both K5 and Sts. Sts, but not K5, failed to induce AVD in cerebellar granule neurons from NOX2 knockout mice. These findings suggest that K5- and Sts-induced AVD is largely mediated by ROS produced by NOX. On the other hand, we also found that the blockage of ionic fluxes involved in AVD inhibited both ROS generation and NOX activity. These findings suggest that ROS generation and NOX activity are involved in ionic fluxes activation, which in turn could maintain ROS generation by activating NOX, leading to a self-amplifying cycle.

Original languageEnglish (US)
Pages (from-to)654-664
Number of pages11
JournalJournal of neurochemistry
Volume117
Issue number4
DOIs
StatePublished - May 2011

Keywords

  • NADPH oxidase
  • apoptosis
  • apoptotic volume decrease
  • ionic fluxes
  • potassium deprivation
  • staurosporine

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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