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Leptin showed different apoptosis regulation effects on the chondrocytes from tibial and vertebral epiphyseal plates. However, the mechanism is still unclear. In this study, we tested the protein profile of tibial and vertebral epiphyseal plate chondrocytes with and without leptin stimulation by mass spectrometry and found that the histone acetylation level of tibial chondrocytes was decreased after leptin treatment, while increased in vertebral epiphyseal plates. COIP assay showed that leptin promoted H3, H4 histone acetylation by recruiting CREB binding protein (CBP)/P300 to activate histone acetyl transferases (HATs) activity in vertebral disc chondrocytes. But in tibial plate cartilage cells, leptin did not recruit CBP and p300, thus differently affect the apoptosis of epiphyseal plate chondrocytes. Through explored the mechanism of histone acetylation modulated by leptin, and its effect on cartilage cell apoptosis and cell cycle regulation, This provides a novel target therapy possibility therapeutic approach to for the related disease. [ABSTRACT FROM AUTHOR]

Purpose: HDAC3, which is associated with smurf2, has been shown to be associated with poor prognosis in B-ALL. This study examined the efficacy of targeting HDAC3 combined with MG-132 as a possible therapeutic strategy for B-ALL patients. Methods: Real-time PCR and western blot were used to measure the expression of smurf2 and HDAC3 from B-ALL patients bone marrow samples. Sup-B15 and CCRF-SB cells were treated with MG-132, small interfering RNA of smurf2 or HDAC3. A plasmid designed to up-regulate smurf2 expression was transfected into B-ALL cells. Flow cytometry and western blot were used to measure variation due to these treatments in terms of apoptosis and cell cycle arrest. Results: Expression of Smurf2 and HDAC3 mRNA were inversely related in B-ALL patients. Up-regulation of smurf2 or MG-132 influenced HDAC3, further inhibiting the JAK/signal transducer and activator of transcription 3 (STAT3) signal pathway and inducing apoptosis in B-ALL cells. When we treated Sup-B15 and CCRF-SB cells with siHDAC3 and MG-132 for 24 h, silencing HDAC3 enhanced the apoptosis rate induced by MG-132 in B-ALL cells and further inhibited the JAK/STAT3 pathway. Furthermore, MG-132 was observed to cause G2/M phase arrest in B-ALL cells and inhibited the JAK/STAT3 pathway, leading to apoptosis. Conclusions: Silencing of HDAC3 enhanced the sensitivity of B-ALL cells to MG-132. The combination of targeting HDAC3 and MG-132 may provide a new avenue for clinical treatment of acute B lymphocytic leukaemia and improve the poor survival of leukaemia patients. [ABSTRACT FROM AUTHOR]

Abstract: The Notch1 signaling pathway plays an essential role in cell growth and differentiation. Over-expression of the intracellular Notch1 domain (ICN1) in murine hematopoietic cells is able to induce robust T-cell acute lymphoblastic leukemia (T-ALL) in mice. Here we explored the drug sensitivity of T-ALL cells in two subpopulations of CD8+CD4+ and CD8+CD4− cells in Notch1-induced T-ALL mice. We found that Notch1 induced T-ALL cells could be decreased by chemotherapeutic drug cyclophosphamide (CTX). CD8+CD4− T-ALL cells were more sensitive to CTX treatment than CD8+CD4+ T-ALL cells. The percentage of apoptotic cells induced by CTX treatment was higher in CD8+CD4− T-ALL cells. T-ALL cells were also inhibited by inhibitor of mTORC1 rapamycin. CD8+CD4+ T-ALL cells were more susceptible to rapamycin treatment than CD8+CD4− T-ALL cells. Rapamycin treatment selectively arrested more CD8+CD4+ T-ALL cells at G0 phase of cell cycle. A combination of the two drugs significantly improved overall survival of T-ALL bearing mice when compared with CTX or rapamycin alone. These results indicated that CD8+CD4+ and CD8+CD4− leukemia cell populations had distinct drug sensitivity. [Copyright &y& Elsevier]