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Superoxide‐Dependent Redox Signaling in the Supraoptic Nucleus Is Associated with the Neuroendocrine Response to Water and Electrolyte Imbalance
Author(s) -
Lima Juliana Bezerra Medeiros,
Morais Sharon Del Bem Velloso,
Schlichte Sarah L.,
Debarba Lucas Kniess,
Coletti Ricardo,
Veanholi Vechiato Fernanda M.,
AntunesRodrigues Jose,
Zucker Irving H.,
Zimmerman Matthew C.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.763.1
Subject(s) - reactive oxygen species , chemistry , redox , supraoptic nucleus , intracellular , superoxide , endocrinology , medicine , superoxide dismutase , signal transduction , nucleus , biophysics , oxidative stress , microbiology and biotechnology , biology , biochemistry , enzyme , organic chemistry
In models of altered osmolality and water balance, including two‐day salt loading and water deprivation, previous studies have suggested that intracellular redox signaling in the supraoptic nucleus (SON) contributes to the neuroendocrine response. However, the precise redox‐dependent signaling pathways and reactive oxygen species (ROS) involved in this response remain unclear. Herein, we tested the hypothesis that water deprivation increases specific ROS, particularly superoxide, and stimulates the redox‐sensitive transcription factor, nuclear factor erythroid 2‐related factor 2 (Nrf2) in the SON and that these responses are dependent on the duration of water restriction. To test this hypothesis, we used rodent models deprived of water for 24 and 48 hours (24h WD and 48h WD, respectively). We observed an increase in Nrf2 mRNA in the SON of rodents subjected to 24h WD (Control: 0.84 ± 0.08 vs 24h WD: 1.16 ± 0.09 arbitrary units) suggesting the activation of redox signaling during dehydration. In addition, at 48h WD, levels of hemeoxygenase‐1 (HO‐1), a Nrf2 target gene, were elevated in the SON (Control: 0.98 ± 0.1 vs 48h WD: 1.46 ± 0.1 arbitrary units). HO‐1 activity was also increased at both time points of water restriction ( F 2,34 = 7.718, p < 0.05). To determine if levels of specific ROS are altered during water deprivation, we used the electron paramagnetic resonance (EPR) spectroscopy. After 24h or 48h of water deprivation in C57BL/6 mice, fresh non‐fixed brains were collected and the SON was harvested via micropunch. Superoxide levels were measured in the SON micropunches by EPR. We also measured plasma osmolality and volume. We observed a dehydration period‐dependent increase in superoxide levels (reported at EPR spectra amplitude in arbitrary units) in the SON (Control: 7150 ± 3856; 24h WD: 14240 ± 9931; 48h WD: 15795 ± 7400 arbitrary units/mg of tissue) along with plasma osmolality (Control: 317 ± 2.0; 24h WD: 326.8 ± 1.3; 48h WD: 330.7 ± 1.3 mOsm/kg H 2 O); protein (Control: 3.56 ± 0.16; 24h WD: 4.36 ± 0.16; 48h WD: 3.94 ± 0.14 g/dL plasma); and hematocrit (Control: 35.8 ± 5.1; 24h WD: 42.4 ± 0.9; 48h WD: 45.7 ± 0.9 %). Together, these data suggest that the neuroendocrine system is associated with superoxide‐dependent redox signaling and activation of Nrf2 in the SON to cope with dehydration. Support or Funding Information FAPESP This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .