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Effect of melatonin as HDAC inhibitor on diurnal HDAC expression in isolated neonatal cardiac cells
Author(s) -
Hong Yunkyung,
Lee Sangkil,
Park Sookyoung,
Kim Jooheon,
Hong Yonggeun
Publication year - 2009
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.23.1_supplement.362.4
Subject(s) - trichostatin a , melatonin , endocrinology , medicine , circadian rhythm , histone h3 , gene expression , histone , blockade , chemistry , biology , microbiology and biotechnology , histone deacetylase , gene , receptor , biochemistry
Many biological systems are regulated by an intricate set of feedback loops that oscillate with a circadian rhythmicity of roughly 24 hr. For example, increases in body temperature, heart rate, blood pressure, and cortisol secretion occur early in the day. Histone proteins exist in a delicate balance between acetylated and deacetylated states. Acetylation leads to nucleosomal relaxation and increased expression of numerous genes. Recent work implicates this chromatin remodeling response in hypertrophic growth of the myocardium. trichostatin A(TSA), a potent inhibitor of histone deactylase(HDAC) activity, imposes a dose‐dependent blockade to hypertrophy and fetal gene activation in neonatal cardiac cells. To explore the role of HDAC activation in an in vitro , we studied the effects of TSA, NaB and melatonin in neonatal and H9c2 cells. Chemicals such as TSA and NaB treated neonatal cardiac cells had an increase of global histone H3 and H4(P<0.05), but decrease of these proteins by melatonin(P<0.01). To determine whether these chemicals act as trigger on the expression of H3 and H4 in cells, we studied cardiac cells subjected to RT‐PCR and immunoblot analysis. At 8 hours after treatment of TSA and NaB, the amplitude of expression of H3 and H4 was significantly decreased, and that of melatonin was significantly damped. Strikingly, diurnal variation of H3 and H4 expression were altered by treatment of TSA and NaB, suggesting a role in anticipating and responding to nuclear processes. However, melatonin induced a 4‐8 hour phase shift of H4 protein expression, and rhythmic expression of H3 was amplified. Key words : melatonin, HDAC, cardiac cells, trichostatin A(TSA), NaB. Supported by KRF‐E00344, BioGreen21 Program (#20070401034006) of Rural Development Administration, South Korea.