Protective signalling effect of manganese superoxide dismutase in hypoxia-reoxygenation of hepatocytes

Michal Pardo*, Oren Tirosh

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

This study investigates the mechanism by which MnSOD exerts its protective effect in hypoxia-reoxygenation (H/R) injury in hepatocytes. Following induction of H/R, MnSOD expression and activity levels increased and remained high for over 24 h. Hepatocytes silenced for MnSOD (siMnSOD) demonstrated increased susceptibility to H/R-induced apoptotic cell death and a lower capacity to generate mitochondrial reactive oxygen species. Microarray and real time PCR analysis of gene expression from siMnSOD cells revealed a number of down-regulated protective genes, including hemeoxygenase-1, glutamate-cysteine ligase and Nrf2, a master regulator of cellular adaptation to stress. Decreased Nrf2 protein expression and nuclear translocation were also confirmed in siMnSOD cells. siMnSOD cells showed low glutathione (GSH) content with no oxidation to GSSG, lower lipid peroxidation levels than their controls and lower mitochondrial membrane potential, which all were even more salient after H/R. Therefore, MnSOD appears to act as a signalling mediator for the activation of survival genes following H/R injury in hepatocytes.

Original languageAmerican English
Pages (from-to)1225-1239
Number of pages15
JournalFree Radical Research
Volume43
Issue number12
DOIs
StatePublished - 2009

Bibliographical note

Funding Information:
This research was supported by a grant from the Dor-set Foundation, UK, to O.T.

Keywords

  • Apoptosis
  • Microarray
  • Mitochondrial defense
  • Reactive oxygen species
  • Redox signaling

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