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Earmarking Target‐Specific Redox Trajectories for Wound Healing in Zebrafish
Author(s) -
Aye Yimon
Publication year - 2017
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.31.1_supplement.608.14
Subject(s) - zebrafish , microbiology and biotechnology , biology , function (biology) , phenotype , cytoprotection , oxidative stress , signal transduction , cell signaling , redox , computational biology , chemistry , biochemistry , gene , organic chemistry
Across the vertebrate lifespan, numerous natural and environmental cues, including reactive electrophilic signals, orchestrate stage‐dependent stress responses that confer cytoprotection. These redox‐linked regulatory mechanisms are choreographed with precise timing and cell type and organ specificity. Yet the molecular players and mechanisms affording the exquisite spatiotemporal control required to mount these responses remain poorly defined. This is in spite of the emerging clinical significance of electrophilic small molecules that modulate specific cytoprotective pathways of conserved importance across animal taxa. Many signaling pathways exert gain‐of‐function effects on target proteins that in turn trigger beneficial signaling responses. Our recent cell‐based studies into the effects of single‐protein‐specific redox events showed that redox‐linked cellular responses can function similarly: low‐stoichiometric redox modifications at a single signaling node can trigger a phenotypic response , implying that novel redox sensor proteins are present in the cell. Using zebrafish as a model system, we now develop a unique unbiased approach to capture redox sensor(s) that function as “first responders”. These proteins would be highly electrophile‐reactive and hence able to elicit pathway activation when only basal amounts of reactive signals are released on‐demand at a specific time and locale. With our zebrafish ‐validated toolset, we identify organ‐specific genuine sensors sufficient and necessary to elicit precisely timed redox responses in live fish embryos that ultimately drive phenotypic responses such as wound healing. Our unique chemical biology platform sets the stage for ruling in gain‐of‐function redox modifications and relating them to phenotype in an unbiased experiment that is not hampered by functional redundancy. Support or Funding Information The NSF CAREER, NIH Director's New Innovator, Beckman Young Investigator, and Sloan Fellowship programs are acknowledged for research support.