A human neuroblastoma cell line, NB-1, was treated with 24 h of microgravity simulation by clinostat, or irradiated with extremely small X-ray doses of 0.1 or 1.0 mGy using single and 10 times fractionation regimes with 1 and 2 h time-intervals. A quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) examination was performed for apoptosis related factors (BAX, CYTC, ...

Apoptosis in metazoans is executed by a group of intracellular proteases named caspases. One of the caspase-activating pathways in mammals is initiated by the release of cytochrome c from mitochondria to cytosol, where it binds to Apaf-1 to form a procaspase-9-activating heptameric protein complex named apoptosome. We report here the reconstitution of this pathway with purified recombinant Apaf...

Background: Myelodysplastic syndromes (MDSs) include a diverse group of clonal bone marrow disorders characterized by ineffective hematopoiesis and pancytopenia. It was found that down regulation of APAF1, a putative tumor suppressor gene (TSG), leads to resistance to chemotherapy and disease development in some cancers. In this study, we investigated the relation of APAF1 methylation status wi...

Mulberry, which contained high amounts of anthocyanins, has been used in traditional Chinese medicine. Mulberry fruit extracts (ME) have demonstrated the antioxidant activity and neuroprotection. The study was to investigate the neuroprotective efficacy of ME against β-amyloid 25-35- (Aβ 25-35-) induced PC12 cells injury. Cells preincubated with or without ME (200 μg/mL) for 24 h were treated w...

Apaf-1 plays an essential role in apoptosis. In the presence of cytochrome c and dATP, Apaf-1 assembles into an oligomeric apoptosome, which is responsible for the activation of procaspase-9 and the maintenance of the enzymatic activity of the processed caspase-9. Regulation of apoptosome assembly by other cellular factors is poorly understood. Here we report that physiological concentrations o...

The apoptotic protease-activating factor 1 (Apaf-1) receives the death signal in the intrinsic ormitochondrial pathway of apoptosis. Upon the releasing of cytochrome c from theintermembrane space of mitochondria and binding to Apaf-1 molecules, a heptamericapoptosome complex is formed and triggers the downstream cascade of caspases. Here, for thefirst time we present spontaneous mutations and r...

Four tumour suppressor genes (Chk1, Chk2, Apaf1 and Rb1) in nine human malignant melanoma cell lines were screened for a loss of gene expression, point mutations and small deletions/insertions by cDNA-based DGGE/SCCP analysis. In two cell lines alterations of the investigated genes could be demonstrated. This result confirms our assumption of the participation of dysfunctional p53 inducer/effec...

Background: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder characterized by immature myeloid cell proliferation and bone marrow failure. Various genetic and epigenetic factors have been found to be influential in such patients. Methylation silencing of APAF-1, a putative tumor suppressor gene (TSG), has been found in several human malignancies. In this study, we explored the as...

A multistep model has been proposed of disease progression starting in monoclonal gammopathy of undetermined significance continuing through multiple myeloma, sometimes with an intermediate entity called smoldering myeloma, and ending in extramedullary disease. To gain further insights into the role of the transcriptome deregulation in the transition from a normal plasma cell to a clonal plasma...

The tumor suppressor gene p53 controls cellular response to a variety of stress conditions, including DNA damage and hypoxia, leading to growth arrest and/or apoptosis. Inactivation of p53, found in 40-50% of human cancers, confers selective advantage under hypoxic microenvironment during tumor progression. The mole rat, Spalax, spends its entire life cycle underground at decidedly lower oxygen...