Involvement of p53 Acetylation in Growth Suppression of Cutaneous T-Cell Lymphomas Induced by HDAC Inhibition
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Authors: Yu, Xiaoxuan; Li, Hui; Zhu, Mengyuan; Hu, Po; Liu, Xiao; Qing, Yingjie; Wang, Xiangyuan; Wang, Hongzheng; Wang, Zhanyu; Xu, Jingyan; Tan, Renxiang; Guo, Qinglong; Hui, Hui
Abstract
Cutaneous T-cell lymphomas (CTCLs) represent a rare form of non-Hodgkin lymphomas characterized by an accumulation of malignant CDC thorn T cells in the skin. TP53 genetic alteration is one of the most prevalent genetic abnormalities in CTCLs. Therefore, it is a promising target for innovative therapeutic approaches. We found that p53 could physically interact with histone deacetylase (HDAC) 1 and HDAC8, and was subsequently deacetylated to lose its function in CTCL cells, and the p53 downstream apoptosis-associated genes were repressed. Thus, the anti-CTCL activity displayed by HDAC inhibitors depends on p53 status. However, recent studies have reported that HDAC inhibitors could induce a wide variety of drug-resistant characteristics in cancer cells by regulating ATP-binding cassette transporters. Moreover, we discovered that Baicalein, a natural product, exhibited an inhibitory effect on HDAC1 and HDAC8. Though the inhibition of HDAC1 was mild, Baicalein could induce the degradation of HDAC1 through the ubiquitin proteasome pathway, thereby markedly upregulating the acetylation of histone H3 without promoting ATP-binding cassette transporter gene expression. In terms of the mechanism, Baicalein showed better growth inhibition than traditional HDAC inhibitors in CTCLs. This study indicates a special mechanism of HDAC1 and HDAC8 and p53 in T-cell lymphoma cells and identifies a potential and safe natural HDAC inhibitor for the treatment of CTCLs.
Taurine modulates protein turnover in several tissues of meagre juveniles
AQUACULTURE
Authors: Matias, Ana Catarina; Dias, Jorge; Barata, Marisa; Araujo, Ravi Luna; Braganca, Jose; Pousao-Ferreira, Pedro
Abstract
This study aimed to evaluate the modulatory effect of dietary taurine supplementation on protein turnover of meagre juveniles fed semi-purified plant-based diets. For that purpose, fish (3.2 +/- 0.2 g) were fed with five isoproteic (61.2%), isolipidic (16.6%) and isoenergetic (21.9 kJ g(-1)) experimental diets supplemented with 0.5% (Tau0.5), 1% (Tau1), 1.5% (Tau1.5) and 2% (Tau2) taurine or not (Tau0) for 38 days. The resulting growth parameters, protein expression levels and the activity of several proteolytic markers involved in the two major degradation pathways in vertebrates (autophagy-lysosomal and ubiquitin-proteasome) were assessed in the liver, intestine and white muscle of meagre. Increasing dietary taurine concentrations promoted fish growth, feed utilization and whole-body protein, lipid and energy contents. Dietary taurine seemed to modulate the activity of cathepsins D and B in white muscle and cathepsin L in the liver. Although, no significant effects were observed on proteasome activity, 1% dietary taurine supplementation decreased the expression of the Psmb4 proteasome subunit in the liver of fish when compared to lower taurine concentrations. No taurine effects were detected on the proteolytic markers analysed in the intestine of meagre. Hsp70 expression levels were also not affected by any of the experimental dietary taurine concentrations. Overall, experimental diet Tau2 promoted the highest growth rate which can be explained by a significant decrease in protein degradation in the liver and white muscle preferentially via the autophagy-lysosomal pathway (cathepsins) over the ubiquitin-proteasome route.