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YB‐1 mediates fetal gene reprogramming during cardiac stress
Author(s) -
Strauch Arthur Roger,
Willis William L.,
David Jason J.
Publication year - 2010
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.24.1_supplement.lb591
Subject(s) - chemistry , fetus , gene expression , myocyte , morpholino , gene knockdown , microbiology and biotechnology , biochemistry , gene , biology , pregnancy , genetics
Fetal smooth muscle alpha‐actin (SMA) is re‐expressed in adult cardiomyocytes in response to biomechanical stress. Transglutaminase 2 (TG2) is associated with myocardial fibrosis and catalyzes gamma‐glutamyl‐peptide linkages via a transamidation reaction in response to reactive oxygen. TG2 was expressed in ventricular cardiomyocytes after ischemia/reperfusion (I/R) injury. Amino‐ and carboxyl‐terminal sequences in the mRNA‐binding, stress granule protein YB‐1 are homologous to TG2 consensus crosslinking motifs. Myocytes exposed to a biotin‐pentylamine TG2 substrate formed biotin‐tagged 50 and 100 kDa YB‐1 variants in the presence of TG2‐activating hydrogen peroxide. Studies using recombinant YB‐1 (rYB‐1) as a TG2 substrate revealed substantial formation of YB‐1 oligomers in the range of 150–250 kDa which varied as a function of rYB‐1 concentration and enhanced in the presence of SMA mRNA. Endomyocardial biopsies collected from patients more than 9 years after heart transplant showed elevated expression of both fetal SMA and low (50 kDa) and high (180 kDa) molecular weight YB‐1:SMA mRNA complexes. YB‐1 deposition also was noted at cardiac intercalated discs after I/R injury. We conclude that TG2‐mediated transamidation of YB‐1 monomers may be potentially important for regulating fetal gene mRNA stability and translational efficiency in the stress‐injured heart. Supported by NIH HL085109.