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Regulation of Extracellular IGFBP‐3 by Humanin in A549 Cells
Author(s) -
Muterspaugh Robert Dean,
Price Deanna,
Guthrie Jeffrey,
Heyl Deborah,
Evans Hedeel
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.804.19
Subject(s) - a549 cell , extracellular , microbiology and biotechnology , biology , cell growth , carcinogenesis , apoptosis , cancer research , biochemistry , gene
The insulin‐like growth factor binding protein 3 (IGFBP3) is a multifunctional protein that belongs to a family of IGF binding proteins with highly conserved structures. Previously, an inverse relationship was demonstrated between serum or plasma levels of the protein and lung cancer risk. The protein was found to inhibit the growth and survival of non‐small cell lung cancer (NSCLC) A549 cells and its overexpression potently induced apoptosis in these cells. Humanin is a small mitochondrial‐derived peptide known to bind with high affinity to residues 242–259 of IGFBP‐3. Growing evidence suggests that, when secreted, humanin is a potent cytoprotective peptide against a range of disease models and cellular stress. The role that humanin plays in tumorigenesis and metastasis is not clear in A549 cells. While both IGFBP‐3 and humanin are known to exert their function both intracellularly and extracellularly, little is known about their extracellular interaction and regulation of A549 cell survival. Our hypothesis is that humanin acts as an IGFBP‐3 sponge in the extracellular compartment and thereby regulates cell growth and survival in a time and concentration dependent manner. Using peptide synthesis, ELISA, immunoprecipitation, Western blotting, and tissue culture, we examine the physical and functional interaction of extracellular IGFBP3 and humanin both in vitro and in vivo in A549 cells. Support or Funding Information This work was supported by an Eastern Michigan University Provost Research Support Award/Chemistry Seller's Fund This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .