Topoisomerase II alpha (TopoIIalpha) and Topoisomerase II beta (TopoIIbeta) isoforms are different gene products having conserved catalytic activities. The alpha isoform is present in proliferating cell, while beta isoform is predominantly present in non-proliferating cells namely neurons suggesting its role in non-replicating functions of DNA. The functions of TopoIIalpha and TopoIIbeta isoforms are analyzed in peroxide-mediated DNA damage and double strand breaks (DSBs) repair in neuroblastoma and astrocytoma cells. The results show a strong correlation of TopoIIalpha level with the progression of DNA damage, while the TopoIIbeta expression is correlated with the DNA DSBs repair activity of cells in Ku70, Werner's helicase and pol-beta dependent pathways. The functional roles of TopoIIalpha and TopoIIbeta are assessed using siRNA mediated TopoIIalpha and TopoIIbeta knockdown in cells. The results show that TopoIIalpha-TopoIIbeta+ cells are resistant to peroxide-mediated DNA damage, while TopoIIalpha+TopoIIbeta- cells are 2-fold more sensitive to peroxide and TopoIIbeta deficiency lead to cellular apoptosis. These results are correlated with cell survival from peroxide-mediated insult. The result of this study that TopoIIalpha accelerates peroxide-mediated DNA damage, while TopoIIbeta promotes DNA DSBs repair activity should provide new directions toward understanding of normalytic ageing processes in human brain.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.abb.2007.10.017 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Ergothioneine, a New Acrolein Scavenger at Elevated Temperature.
J Agric Food Chem
January 2025
Department of Food Science and Technology, School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, 2# Xuelin Road, Nanjing 210023, People's Republic of China.
Acrolein (ACR) present in vivo and in vitro can damage proteins and DNA, linking it to various chronic diseases. In this paper, ergothioneine (EGT), abundant in edible mushrooms, has been studied for its ability to trap ACR and its reaction pathway with ACR at high temperatures using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS). We synthesized the adducts (EGT-ACR-1 and EGT-ACR-2), elucidating their structure and reaction site through HRMS and nuclear magnetic resonance.
View Article and Find Full Text PDFDNA-Dependent Protein Kinase Catalytic Subunit Prevents Ferroptosis in Retinal Pigment Epithelial Cells.
Invest Ophthalmol Vis Sci
January 2025
Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, China.
Purpose: The purpose of this study was to investigate the activated core kinases involved in the DNA damage responses (DDR) during ferroptosis of retinal pigment epithelial (RPE) cells in vitro and their regulatory effects on ferroptosis.
Methods: Ferroptosis was induced by erastin in induced RPE (iRPE) cells derived from human umbilical cord mesenchymal stem cells (hUCMSCs), hUCMSCs, and induced pluripotent stem cell-derived RPE (iPSC-RPE) cells. CCK8 was employed to measure the cell viability.
Colorectal carcinoma (CRC) progression is associated with an increase in PROX1+ tumor cells, which exhibit features of CRC stem cells and contribute to metastasis. Here, we aimed to provide a better understanding to the function of PROX1+ cells in CRC, investigating their progeny and their role in therapy resistance. PROX1+ cells in intestinal adenomas of ApcMin/+ mice expressed intestinal epithelial and CRC stem cell markers, and cells with high PROX1 expression could both self-renew tumor stem/progenitor cells and contribute to differentiated tumor cells.
View Article and Find Full Text PDFWhile key for pathogen immobilization, neutrophil extracellular traps (NETs) often cause severe bystander cell/tissue damage. This was hypothesized to depend on their prolonged presence in the vasculature, leading to cytotoxicity. Imaging of NETs (histones, neutrophil elastase, extracellular DNA) with intravital microscopy in blood vessels of mouse livers in a pathogen-replicative-free environment (endotoxemia) led to detection of NET proteins attached to the endothelium for months despite the early disappearance of extracellular DNA.
View Article and Find Full Text PDFMineral Stress Drives Loss of Heterochromatin: An Early Harbinger of Vascular Inflammaging and Calcification.
Circ Res
January 2025
British Heart Foundation Centre for Research Excellence, School of Cardiovascular and Metabolic Medicine and Sciences, James Black Centre, King's College London, United Kingdom (C.Y.H., M.-Y.W., J.T., S.A., L.D., G.A., R.H., C.M.S.).
Background: Vascular calcification is a detrimental aging pathology markedly accelerated in patients with chronic kidney disease. Prelamin A is a biomarker of vascular smooth muscle cell aging that accelerates calcification however the mechanisms remain undefined.
Methods: Vascular smooth muscle cells were transduced with prelamin A using an adenoviral vector and epigenetic modifications were monitored using immunofluorescence and targeted polymerase chain reaction array.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!