Protective role of MnSOD and redox regulation of neuronal cell survival

T. Galeotti, G. Pani, C. Capone, B. Bedogni, S. Borrello, C. Mancuso, M. L. Eboli

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Reactive oxygen species (ROS) play a central role in neuronal pathophysiology and in neurodegenerative disorders. However, recent evidence indicates that these molecules also operate as signaling intermediates in a variety of physiological settings, including cell protection from apoptosis. Data presented here strongly support such a dual role for oxidants in neuronal cell homeostasis. In rat pheocromocytoma cells, cell rescue by the nerve growth factor (NGF) is accompanied by a transient burst of ROS generated in the cytosol by a GTPase-dependent mechanism. Within the NGF signaling cascade, ROS lie upstream and are necessary for activation/phosphorylation of AKT/PKB and of the antiapoptotic transcription factor cAMP-responsive element-binding protein (CREB). Conversely, an increase in mitochondrial oxygen species heralds apoptosis of serum-deprived cells, and these events can be prevented by cell exposure to NGF or by treatment with the mitochondrially targeted antioxidant MitoQ. Importantly, NGF-mediated decrease of mitochondrial ROS is dependent on the transcriptional up-regulation of the manganese superoxide dismutase (MnSOD) by active CREB. These observations therefore outline a circuitry whereby cytosolic redox signaling promotes neuronal cell survival by increasing the mitochondrial antioxidant defenses.

Original languageEnglish (US)
Pages (from-to)197-203
Number of pages7
JournalBiomedicine and Pharmacotherapy
Volume59
Issue number4
DOIs
StatePublished - May 2005
Externally publishedYes

Keywords

  • CREB transcription Factor
  • Manganese Superoxide Dismutase (MnSOD)
  • Nerve Growth Factor (NGF)
  • Reactive Oxygen Species (ROS)

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Galeotti, T., Pani, G., Capone, C., Bedogni, B., Borrello, S., Mancuso, C., & Eboli, M. L. (2005). Protective role of MnSOD and redox regulation of neuronal cell survival. Biomedicine and Pharmacotherapy, 59(4), 197-203. https://doi.org/10.1016/j.biopha.2005.03.002