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09:03
Analysis of Human Natural Killer Cell Metabolism
Published on: June 22, 2020
NAD kinase levels control the NADPH concentration in human cells
Nadine Pollak1, Marc Niere1, Mathias Ziegler1
1Department of Molecular Biology, University of Bergen, Thormøhlensgate 55, N-5008 Bergen, Norway.
The Journal of Biological Chemistry
|September 15, 2007
Summary
Human cells rely on NADP-dependent dehydrogenases, not just NAD kinases (NADK), to manage oxidative stress. This study reveals how altering NADK impacts NADPH levels and cellular defense mechanisms.
Area of Science:
- Biochemistry
- Cell Biology
- Oxidative Stress
Background:
- NAD kinases (NADKs) are crucial for generating the cellular NADP pool.
- Mammals possess a single NADK, localized in the cytoplasm, unlike plants and yeast with multiple isoforms.
Purpose of the Study:
- To investigate the physiological roles of the human NADK enzyme.
- To understand the impact of NADK modulation on cellular NADPH levels and oxidative stress response.
Main Methods:
- Generation and analysis of cell lines with stable NADK deficiency or overexpression.
- Immunocytochemistry to confirm cytoplasmic localization of human NADK.
- Short hairpin RNA (shRNA) for gene down-regulation.
Main Results:
- NADK down-regulation decreased NADK expression, activity, and NADPH concentration by ~70%, increasing H(2)O(2) sensitivity.
- NADK overexpression increased NADPH levels 4-5 fold but not NADP(+), despite preferential NAD(+) phosphorylation by the enzyme.
- Enhanced NADPH levels offered only moderate protection against oxidants, suggesting a primary role for NADP-dependent dehydrogenases in redox homeostasis.
Conclusions:
- Human cells primarily utilize NADP-dependent dehydrogenases for NADPH regeneration in oxidative defense.
- Cellular NADP redox state may act as a key signaling pathway for oxidative stress.
- NADK modulation influences peroxiredoxin 5 and Nrf2 expression.
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