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Prolonged fasting activates Nrf2 in post-weaned elephant seals
José Pablo Vázquez-Medina1, José G Soñanez-Organis, Ruben Rodriguez
1School of Natural Sciences, University of California Merced, Merced, CA, USA. jvazquez-medina@ucmerced.edu
The Journal of Experimental Biology
|April 27, 2013
Summary
Elephant seals activate antioxidant defenses during fasting by increasing the transcription factor Nrf2, potentially mediated by the renin-angiotensin system (RAS). This protects them from oxidative damage, unlike other mammals.
Area of Science:
- Physiology
- Molecular Biology
- Comparative Biology
Background:
- Prolonged fasting in mammals activates the renin-angiotensin system (RAS) and increases oxidative damage.
- Elephant seals fast for extended periods but do not exhibit increased oxidative damage, suggesting enhanced antioxidant defenses.
- The mechanism for upregulated antioxidant defenses during fasting in elephant seals is unknown.
Purpose of the Study:
- To investigate if prolonged fasting activates the transcription factor Nrf2 in elephant seals.
- To determine if RAS activation mediates Nrf2 activation during fasting.
- To explore the role of NADPH oxidase 4 (Nox4) in the adaptive response to fasting.
Main Methods:
- Collected blood and skeletal muscle samples from elephant seals fasting for 1, 3, 5, and 7 weeks.
- Measured Nrf2 activity and nuclear content.
- Assessed plasma levels of angiotensin II (Ang II) and transforming growth factor β (TGF-β).
- Analyzed Smad2 phosphorylation and NADPH oxidase 4 (Nox4) mRNA and protein expression.
Main Results:
- Nrf2 activity and nuclear content significantly increased by week 7 of fasting.
- Plasma Ang II and TGF-β levels were markedly elevated at week 7.
- Smad2 phosphorylation increased, correlating with Ang II infusion and elevated at week 7.
- Nox4 mRNA and protein expression showed significant increases by week 7.
Conclusions:
- Prolonged fasting activates Nrf2 in elephant seals, enhancing antioxidant defenses.
- RAS stimulation appears to mediate increased Nox4 expression via Smad phosphorylation.
- Nox4 is crucial for the hormetic adaptive response to oxidative stress during fasting in seals.
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