RESUMEN
HDAC8, a member of class I HDACs, plays a pivotal role in cell cycle regulation by deacetylating the cohesin subunit SMC3. While cyclins and CDKs are well-established cell cycle regulators, our knowledge of other regulators remains limited. Here we reveal the acetylation of K202 in HDAC8 as a key cell cycle regulator responsive to stress. K202 acetylation in HDAC8, primarily catalyzed by Tip60, restricts HDAC8 activity, leading to increased SMC3 acetylation and cell cycle arrest. Furthermore, cells expressing the mutant form of HDAC8 mimicking K202 acetylation display significant alterations in gene expression, potentially linked to changes in 3D genome structure, including enhanced chromatid loop interactions. K202 acetylation impairs cell cycle progression by disrupting the expression of cell cycle-related genes and sister chromatid cohesion, resulting in G2/M phase arrest. These findings indicate the reversible acetylation of HDAC8 as a cell cycle regulator, expanding our understanding of stress-responsive cell cycle dynamics.
RESUMEN
Jujube contains abundant cyclic adenosine monophosphate (cAMP). In contrast, the extraction technology of cAMP from jujube is still to be explored. In this study, the ultra-high pressure extraction (UHPE) conditions for obtaining the maximum cAMP yield from jujube were optimized. Orthogonal array design (OAD) was applied to evaluate the effects of three variables (pressure, pressure-holding time, and liquid-to-solid ratio) by UHPE on cAMP yield. The results showed that the optimal cAMP yield (1223.2 µg/g) was derived at 300 MPa, 20 min duration, and a liquid-to-solid ratio of 2.5 ml/g. In addition, as an important functional ingredient in jujube, cAMP has potential anti-allergic effect. To develop the functional characteristics of jujube, the effect of cAMP was characterized in vivo with the Balb/c mouse model of peanut allergy, which was established by subcutaneous injection of crude peanut protein extract (PN). The results showed that treatment with cAMP in PN-sensitized mice suppressed the lesions in jejunal tissues and allergic symptoms and restored spleen index. Meanwhile, cAMP treatment reduced serum levels of specific immunoglobulin E (IgE), histamine, as well as interleukin-4 (IL-4) and stimulated the secretion of tumor necrosis factor-α (TNF-α), whereas the serum levels of interleukin-10 (IL-10) were not affected. Our results suggested that cAMP has an anti-allergic effect in PN-sensitized mice.