Pharmacological modulation of histone demethylase activity by a small molecule isolated from subcritical water extracts of <it>Sasa senanensis</it> leaves prolongs the lifespan of <it>Drosophila melanogaster</it>
<p>Abstract</p> <p>Background</p> <p>Extracts of <it>Sasa senanensis</it> Rehder are used in traditional Japanese medicine; however, little is known about the underlying mechanisms of their potential health benefits.</p> <p>Methods</p> <...
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| Main Authors: | , , , , , , , |
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| Format: | Book |
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BMC,
2012-07-01T00:00:00Z.
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| Summary: | <p>Abstract</p> <p>Background</p> <p>Extracts of <it>Sasa senanensis</it> Rehder are used in traditional Japanese medicine; however, little is known about the underlying mechanisms of their potential health benefits.</p> <p>Methods</p> <p><it>S. senanensis</it> leaves were extracted with subcritical water. An active small-molecule was isolated using reversed-phase high-performance liquid chromatography (HPLC), and identified as 3,4-dihydroxybenzaldehyde (protocatechuic aldehyde or PA). The effects of PA on the activity of histone demethylase, the <it>Drosophila melanogaster</it> lifespan and gene expression in <it>Drosophila</it> S2 cells were investigated.</p> <p>Results</p> <p>PA inhibited the activity of Jumonji domain-containing protein 2A (JMJD2A) histone demethylase in a dose-dependent manner with a half-maximal inhibitory concentration (IC<sub>50</sub>) of 11.6 μM. However, there was no effect on lysine-specific demethylase 1 (LSD1), histone deacetylase 1 (HDAC1) or HDAC8. PA significantly extended the lifespan of female, but not male, <it>Drosophila</it>. In <it>Drosophila</it> S2 cells, the eukaryotic translation initiation factor 4E binding protein (4E-BP) was up-regulated by PA exposure.</p> <p>Conclusions</p> <p>Our findings provide insight into the possible relationship between the pharmacological modulation of histone demethylation and lifespan extension by PA; they might also be important in the development of alternative therapies for age-related disorders.</p> |
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| Item Description: | 10.1186/1472-6882-12-101 1472-6882 |