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Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
A systems biology perspective on Nrf2-mediated antioxidant response
Qiang Zhang1, Jingbo Pi, Courtney G Woods
1Division of Computational Biology, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709, USA. qzhang@thehamner.org
Toxicology and Applied Pharmacology
|September 1, 2009
Summary
Cells use antioxidant enzymes to combat reactive oxygen species (ROS) but over-activation may disrupt vital ROS signaling, potentially causing disease. This suggests dietary antioxidants may not always be beneficial.
Area of Science:
- Cellular Biology
- Systems Biology
- Biochemistry
Background:
- Cells are constantly exposed to reactive oxygen species (ROS) from internal and external sources.
- Antioxidant enzymes protect cells from ROS damage by scavenging these molecules and restoring redox homeostasis.
- The adaptive response to oxidative stress involves a redox-sensitive gene regulatory network mediated by nuclear factor E2-related factor 2 (Nrf2).
Purpose of the Study:
- To understand the cellular redox control system from a systems engineering perspective.
- To investigate the role of ROS signaling in oxidative stress-induced diseases.
- To re-evaluate the benefits of dietary antioxidant supplements.
Main Methods:
- Systems engineering approaches to analyze the cellular redox control network.
- Decomposition of the redox control system into functional modules (transducer, controller, actuator, plant).
- Analysis of feedback loops, feedforward control, and ultrasensitive signaling motifs.
Main Results:
- The cellular redox control system functions similarly to engineered control devices with distinct modules and feedback mechanisms.
- Over-upregulation of antioxidant enzymes during oxidative stress may attenuate crucial ROS signaling pathways.
- This attenuation can lead to cellular dysfunction and pathological conditions.
Conclusions:
- Oxidative stress can paradoxically lead to disease by disrupting physiological ROS signaling.
- The competing cellular tasks of antioxidant defense and ROS signaling need simultaneous consideration.
- Dietary antioxidant supplements may have adverse effects due to interference with essential ROS signaling.
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