TY - JOUR
T1 - The role of redox modulation of class II histone deacetylases in mediating pathological cardiac hypertrophy
AU - Oka, Shin Ichi
AU - Ago, Tetsuro
AU - Kitazono, Takanari
AU - Zablocki, Daniela
AU - Sadoshima, Junichi
N1 - Funding Information:
Acknowledgment This work was in part supported by US Public Health Service Grants HL 59139, HL67724, HL67727, HL69020, and HL 73048.
PY - 2009/8
Y1 - 2009/8
N2 - Many biological functions in cells are regulated by the effects of the redox state on cellular signaling pathways. In the heart, pathological hypertrophy caused by a wide variety of stimuli is commonly mediated by nucleo-cytoplasmic translocation of class II histone deacetylases (HDACs) and subsequent de-suppression of transcription factors, including nuclear factor of activated T-cells and MEF2. One of the primary triggers of class II HDAC nuclear export is phosphorylation by HDAC kinases activated by hypertrophic stimuli. However, oxidative modification of conserved cysteine residues can also potentially induce nuclear export of class II HDACs. Thioredoxin 1 (Trx1), a 12 kDa anti-oxidant, inhibits pathological hypertrophy through reduction of cysteine residues in class II HDACs. In this review, we discuss the role of posttranslational modification of class II HDACs in mediating cardiac hypertrophy and the molecular mechanism by which Trx1 inhibits pathological cardiac hypertrophy.
AB - Many biological functions in cells are regulated by the effects of the redox state on cellular signaling pathways. In the heart, pathological hypertrophy caused by a wide variety of stimuli is commonly mediated by nucleo-cytoplasmic translocation of class II histone deacetylases (HDACs) and subsequent de-suppression of transcription factors, including nuclear factor of activated T-cells and MEF2. One of the primary triggers of class II HDAC nuclear export is phosphorylation by HDAC kinases activated by hypertrophic stimuli. However, oxidative modification of conserved cysteine residues can also potentially induce nuclear export of class II HDACs. Thioredoxin 1 (Trx1), a 12 kDa anti-oxidant, inhibits pathological hypertrophy through reduction of cysteine residues in class II HDACs. In this review, we discuss the role of posttranslational modification of class II HDACs in mediating cardiac hypertrophy and the molecular mechanism by which Trx1 inhibits pathological cardiac hypertrophy.
UR - http://www.scopus.com/inward/record.url?scp=70349251897&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70349251897&partnerID=8YFLogxK
U2 - 10.1007/s00109-009-0471-2
DO - 10.1007/s00109-009-0471-2
M3 - Review article
C2 - 19424677
AN - SCOPUS:70349251897
SN - 0946-2716
VL - 87
SP - 785
EP - 791
JO - Journal of Molecular Medicine
JF - Journal of Molecular Medicine
IS - 8
ER -