AGE

, Volume 34, Issue 2, pp 359–370

The plasma membrane redox enzyme NQO1 sustains cellular energetics and protects human neuroblastoma cells against metabolic and proteotoxic stress

  • Dong-Hoon Hyun
  • Jiyeong Kim
  • Chanil Moon
  • Chang-Jin Lim
  • Rafael de Cabo
  • Mark P. Mattson
Article

DOI: 10.1007/s11357-011-9245-1

Cite this article as:
Hyun, DH., Kim, J., Moon, C. et al. AGE (2012) 34: 359. doi:10.1007/s11357-011-9245-1

Abstract

The plasma membrane redox system (PMRS) of nicotinamide adenine dinucleotide (NADH)-related enzymes plays a key role in the maintenance of cellular energetics. During the aging process, neural cells are particularly sensitive to impaired energy metabolism and oxidative damage, but the involvement of the PMRS in these processes is unknown. Here, we used human neuroblastoma cells with either elevated or reduced levels of the PMRS enzyme NADH-quinone oxidoreductase 1 (NQO1) to investigate how the PMRS regulates neuronal stress responses. Cells with elevated NQO1 levels were more resistant to death induced by 2-deoxyglucose, potassium cyanide (energetic stress), and lactacystin (proteotoxic stress), but were not protected from being killed by H2O2 and serum withdrawal. The NAD+(an oxidized form of NADH)/NADH ratio was maintained at a significantly higher level in cells overexpressing NQO1, consistent with enhanced levels of NQO1 activity. Levels of the neuroprotective transcription factors nuclear factor kappa-light-chain-enhancer of activated B cells and nuclear factor (erythroid-derived 2)-like 2, and the protein chaperone HSP70 were elevated in cells overexpressing NQO1. Cells in which NQO1 levels were decreased by RNA interference exhibited increased vulnerability to death induced by 2-deoxyglucose and lactacystin. Thus, a higher NAD+/NADH ratio and activation of adaptive stress response pathways are enhanced by the PMRS in neuroblastoma cells, enabling them to maintain redox homeostasis under conditions of energetic and proteotoxic stress. These findings have implications for the development of therapeutic interventions for neural tumors and neurodegenerative conditions.

Keywords

Aging NAD+/NADH Neuroprotection NQO1 PMRS Proteotoxicity 

Copyright information

© American Aging Association 2011

Authors and Affiliations

  • Dong-Hoon Hyun
    • 1
  • Jiyeong Kim
    • 1
  • Chanil Moon
    • 2
  • Chang-Jin Lim
    • 3
  • Rafael de Cabo
    • 4
  • Mark P. Mattson
    • 5
  1. 1.Division of Life and Pharmaceutical Sciences, Department of Life ScienceEwha Womans UniversitySeoulSouth Korea
  2. 2.Cell Therapy CenterHanyang Univeristy Seoul HospitalSeoulSouth Korea
  3. 3.Division of Life SciencesKangwon National UniversityChuncheonSouth Korea
  4. 4.Laboratory of Experimental GerontologyNational Institute on Aging Intramural Research Program, National Institutes of HealthBaltimoreUSA
  5. 5.Laboratory of NeurosciencesNational Institute on Aging Intramural Research Program, National Institutes of HealthBaltimoreUSA

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