Degradation of chromatin modifiers, histone deacetylases, by Spirulina platensis extracts in macrophages (1045.11)

Abstract

The roles of dietary components in the modulation of chromatin modifiers, such as histone deacetylases (HDACs), to control gene transcription are largely unknown. We previously demonstrated that the organic extract of Spirulina platensis (SPE), a blue‐green alga, potently inhibited the expression and secretion of pro‐inflammatory mediators in macrophages. Therefore, the objective of our study was to investigate whether SPE ameliorates inflammation through the modulation of HDACs. We found that SPE facilitated rapid degradation of HDAC2, 4 and 9 in a time and dose‐dependent manner in RAW 264.7 macrophages. More specifically, HDAC4 was more labile and sensitive to SPE when compared to HDAC2. The increased HDAC degradation by SPE was not unique to RAW 264.7 macrophages, but also occurred in bone marrow‐derived macrophages and other cell lines. Inhibition of proteasomes, lysosomal acidification, or calpain proteases with MG132 (10 μM), chloroquine (50 μM), or calpeptin (20 μg/mL), respectively, revealed that SPE facilitated the degradation of HDAC4 at least partly via lysosomes and calpain proteases, but not proteasomes. In contrast, the degradation of HDAC2 by SPE was not attenuated by the inhibitors. Our results demonstrate that SPE can regulate the protein levels of HDACs and therefore might potentially possess an epigenetic mode of action for the regulation of gene transcription.Grant Funding Source: Funded by NIH R21AT005152