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Selective Inhibition of HDAC‐6 is Cardioprotective in an Endothelial Cell/Cardiomyocyte Co‐Culture Model
Author(s) -
Procknow Jesse,
Liu Yanan,
Weihrauch Dorothee,
Pratt Phillip,
Kersten Judy
Publication year - 2012
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.26.1_supplement.lb527
Subject(s) - trichostatin a , histone deacetylase , hypoxia (environmental) , nitric oxide , acetylation , lactate dehydrogenase , chemistry , nitric oxide synthase , enos , western blot , microbiology and biotechnology , pharmacology , histone , biochemistry , medicine , biology , enzyme , organic chemistry , oxygen , gene
The acetylation state of α‐tubulin (αt) regulates nitric oxide synthase‐generated nitric oxide in endothelial cells (EC) and this pathway may be important in protecting against cellular injury. αt is a substrate of histone deacetylase‐6 (HDAC‐6); therefore, EC‐mediated protection of cardiomyocytes could be HDAC‐6‐dependent. Human coronary artery EC were co‐cultured with isolated neonatal rat cardiomyocytes at a 1:6 ratio (CC) and subjected to two hours of hypoxia and two hours of reoxygenation. CC were pretreated for one hour prior to hypoxia with a nonselective [trichostatin A (TSA), 750 nM] or a selective HDAC‐6 inhibitor (tubacin, 50 nM). Hypoxia significantly increased HDAC‐6 expression in cardiomyocytes compared to normoxic controls measured by Western Blot (WB) and immunofluorescence intensity. Compared to control CC, lactate dehydrogenase activity, an index of cell injury, was significantly decreased in CC pretreated with tubacin when compared to TSA‐treated cells or vehicle. Tubacin also increased acetylated αt expression compared to control measured by WB. These results suggest that HDAC‐6 may be involved in cardioprotective signaling by modulating the acetylation state of αt. Future studies will examine the importance of HDAC‐6 in regulating other cardioprotective pathways, such as nitric oxide production. This work was supported by NIH Grant 1 T32 GM089586.