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Research Article
Prolonged fasting activates Nrf2 in post-weaned elephant seals
José Pablo Vázquez-Medina, José G. Soñanez-Organis, Ruben Rodriguez, Jose A. Viscarra, Akira Nishiyama, Daniel E. Crocker, Rudy M. Ortiz
Journal of Experimental Biology 2013 216: 2870-2878; doi: 10.1242/jeb.081927
José Pablo Vázquez-Medina
1School of Natural Sciences, University of California Merced, Merced, CA, USA
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  • For correspondence: jvazquez-medina@ucmerced.edu
José G. Soñanez-Organis
1School of Natural Sciences, University of California Merced, Merced, CA, USA
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Ruben Rodriguez
1School of Natural Sciences, University of California Merced, Merced, CA, USA
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Jose A. Viscarra
1School of Natural Sciences, University of California Merced, Merced, CA, USA
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Akira Nishiyama
2Department of Pharmacology, Kagawa Medical University, Kagawa, Japan
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Daniel E. Crocker
3Department of Biology, Sonoma State University, Rohnert Park, CA, USA
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Rudy M. Ortiz
1School of Natural Sciences, University of California Merced, Merced, CA, USA
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    Fig. 1.

    Prolonged fasting increases plasma levels of angiotensin II (Ang II) and transforming growth factor β (TGF-β) in elephant seal pups. Mean and s.e.m. circulating levels of (A) Ang II and (B) TGF-β1 in elephant seals during their post-weaning fast are shown. *Significantly different from week 1 (P<0.05).

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    Fig. 2.

    Prolonged fasting increases Smad activation in elephant seal pups. Mean and s.e.m. Smad2 phosphorylation (Ser465/467) (phospho-Smad2, P-Smad2 levels) in the skeletal muscle of the elephant seal during its post-weaning fast. A representative blot is shown in the inset. *Significantly different from week 1 (P<0.05).

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    Fig. 3.

    Acute infusion of Ang II stimulates Smad activation in elephant seal pups. (A) Circulating aldosterone levels (mean ± s.e.m.) in response to an acute intravenous infusion of Ang II alone or with angiotensin receptor type 1 blocker (ARB) in post-weaned elephant seals. (B) Mean and s.e.m. phospho-Smad2 (Ser465/467) levels in the skeletal muscle of post-weaned elephant seals in response to acute intravenous infusion of Ang II/Ang II + ARB. A representative blot is shown in the inset (C, control; i, Ang II; ii, Ang II + ARB). *Significantly different from week 1 (P<0.05). See Materials and methods for further details.

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    Fig. 4.

    Elephant seal Nox4 is a conserved enzyme that is distinct from other Nox homolog proteins. (A) Multiple alignment of amino acid sequences of Nox4 proteins. Northern elephant seal (esNox4), domestic dog (XP_542262), giant panda (XP_002927888), rat (NP_445976) and human (AAF68973) predicted amino acid sequences are included in the analysis. Black triangles indicate conserved histidine residues involved in heme–iron binding. Black boxes represent predicted transmembrane α-helices. The putative FAD and NADPH binding sites are indicated. (B) Multiple alignment of amino acid sequences of several Nox homolog proteins. The northern elephant seal Nox4 (esNox4) and human Nox proteins (Hm.gp91phox, NP_000388; Hm.Nox1, CAI42336; Hm.Nox3, AAG17121; Hm.Nox4, AAF68973; and Hm.Nox5, AAG33638) amino acid sequences are included in the analysis. Black boxes represent identical amino acid residues between esNox4 and Hm.Nox4 that differ from other human Nox proteins. The putative FAD and NADPH binding sites are indicated.

  • Fig. 5.
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    Fig. 5.

    Prolonged fasting increases Nox4 expression in elephant seal pups. Mean and s.e.m. Nox4 (A) mRNA and (B) protein expression during prolonged fasting in the skeletal muscle of post-weaned elephant seals. A representative blot is shown in the inset (band densities were normalized to actin). *Significantly different from week 1 (P<0.05).

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    Fig. 6.

    Prolonged fasting activates the Nrf2/electrophilic responsive element (EpRE) pathway in elephant seal pups. Mean and s.e.m. (A) Nrf2 levels in nuclear fractions prepared from skeletal muscle, (B) binding ability of activated Nrf2 to the EpRE consensus binding site and (C) mRNA expression of CuZnSOD during prolonged fasting in post-weaned elephant seals. The inset in A shows a representative blot (band densities were normalized to TATA-binding protein). *Significantly different from week 1 (P<0.05).

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    Fig. 7.

    Schematic representation of the proposed mechanisms leading to the activation of the elephant seal antioxidant system during prolonged fasting.

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Keywords

  • Antioxidants
  • Hormesis
  • Nox4
  • Oxidative stress
  • Starvation
  • renin–angiotensin system

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Research Article
Prolonged fasting activates Nrf2 in post-weaned elephant seals
José Pablo Vázquez-Medina, José G. Soñanez-Organis, Ruben Rodriguez, Jose A. Viscarra, Akira Nishiyama, Daniel E. Crocker, Rudy M. Ortiz
Journal of Experimental Biology 2013 216: 2870-2878; doi: 10.1242/jeb.081927
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Research Article
Prolonged fasting activates Nrf2 in post-weaned elephant seals
José Pablo Vázquez-Medina, José G. Soñanez-Organis, Ruben Rodriguez, Jose A. Viscarra, Akira Nishiyama, Daniel E. Crocker, Rudy M. Ortiz
Journal of Experimental Biology 2013 216: 2870-2878; doi: 10.1242/jeb.081927

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