The inhibitors of protein phosphatase such as calyculin A and okadaic acid induce the apoptotic cell death in rat thymocytes. To clarify the molecular mechanism of these inhibitor-induced apoptosis, the effect of calyculin A on DNA fragmentation in the isolated nuclei were studied. A significant increase in DNA fragmentation was observed in the nuclei prepared from the cells treated with calyculin A that caused histone hyperphosphorylation. No changes of the activities of caspase-8 and -3 were observed in the extract from the cells treated with calyculin A. The circular dichroism analysis of soluble chromatin from calyculin A-treated thymocyte nuclei indicated that phosphorylation of histones decreased its alpha-helical content. Thus, the change in the chromatin structure may be due to the chemical modification of histones. Moreover, the structural change in chromatin preceded DNA fragmentation in the nuclei. Therefore, these results suggest that the change of chromatin structure allow easy accessibility of nuclear DNase to chromosomal DNA.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1080/15216540214536 | DOI Listing |
Acta Neuropathol
January 2025
Department of Neurology, NYU Grossman School of Medicine, New York, NY, USA.
Down syndrome (DS) is strongly associated with Alzheimer's disease (AD) due to APP overexpression, exhibiting Amyloid-β (Aβ) and Tau pathology similar to early-onset (EOAD) and late-onset AD (LOAD). We evaluated the Aβ plaque proteome of DS, EOAD, and LOAD using unbiased localized proteomics on post-mortem paraffin-embedded tissues from four cohorts (n = 20/group): DS (59.8 ± 4.
View Article and Find Full Text PDFHum Mol Genet
January 2025
Department of Human Genetics, McGill University, 3666 McTavish Street, Montreal, QC H3A 1Y2, Canada.
Many genes in the human genome encode proteins that are dosage sensitive, meaning they require protein levels within a narrow range to properly execute function. To investigate if clinically relevant variation in protein levels impacts the same downstream pathways in human disease, we generated cell models of two SETBP1 syndromes: Schinzel-Giedion Syndrome (SGS) and SETBP1 haploinsufficiency disease (SHD), where SGS is caused by too much protein, and SHD is caused by not enough SETBP1. Using patient and sex-matched healthy first-degree relatives from both SGS and SHD SETBP1 cases, we assessed how SETBP1 protein dosage affects downstream pathways in human forebrain progenitor cells.
View Article and Find Full Text PDFUltrastruct Pathol
January 2025
Department of Histochemistry and Cell Biology, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Breast cancer patients experience more severe emotional distress and depression compared to those with other cancers. Selective serotonin reuptake inhibitors (SSRIs), like citalopram, are commonly used to treat depression. However, the link between SSRI use and breast cancer progression is debated.
View Article and Find Full Text PDFCell Biochem Biophys
January 2025
Department of Medical Laboratories Technology, AL-Nisour University College, Baghdad, Iraq.
Histone acetylation is the process by which histone acetyltransferases (HATs) add an acetyl group to the N-terminal lysine residues of histones, resulting in a more open chromatin structure. Histone acetylation tends to increase gene expression more than methylation does. In the central nervous system (CNS), histone acetylation is essential for controlling the expression of genes linked to cognition and learning.
View Article and Find Full Text PDFNat Commun
January 2025
State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China.
Transcription elongation, especially RNA polymerase II (Pol II) pause-release, is less studied than transcription initiation in regulating gene expression during meiosis. It is also unclear how transcription elongation interplays with transcription initiation. Here, we show that depletion of NKAPL, a testis-specific protein distantly related to RNA splicing factors, causes male infertility in mice by blocking the meiotic exit and downregulating haploid genes.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!