Previously, we have found that activation of deoxycytidine kinase elicited by various DNA-damaging chemical agents could be prevented by BAPTA-AM, a cell-permeable calcium chelator or by pifithrin-alpha, a pharmacological inhibitor of p53. Here, we show that stimulation of deoxycytidine kinase by UV-light also is calcium-dependent and pifithrin-alpha-sensitive in tonsillar lymphocytes, while thymidine kinase 1 activity is stabilised in the presence of BAPTA-AM. Importantly, both UV-irradiation and calcium chelation decreased the incorporation of labelled deoxycytidine and thymidine into DNA. Pifithrin-alpha dramatically reduced the labelling of both the nucleotide and DNA fractions, possibly due to inhibition of transmembrane nucleoside transport.
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http://dx.doi.org/10.1080/15257770600894402 | DOI Listing |
Adv Mater
January 2025
Department of Radiology, Huashan Hospital, Fudan University, Shanghai, 200040, P. R. China.
Mesenchymal stem cells (MSCs) transplantation is a promising therapeutic strategy for ischemic stroke. However, the survival of transplanted MSCs is often compromised by the excessive levels of reactive oxygen species (ROS) and calcium ions (Ca) in the ischemic microenvironment following blood flow occlusion. In this study, a protective strategy is developed using functional nanomaterials to escort and shield MSCs.
View Article and Find Full Text PDFJ Mol Cell Cardiol
January 2025
School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China; State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Harbin Medical University, China; Chongqing Key Laboratory of New Drug Delivery System, Chongqing 400038, China. Electronic address:
Background And Aim: Our previous research indicates that sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) dysfunction facilitates the phenotypic transformation of aortic smooth muscle cells (ASMCs) and intensifies aortic aneurysm through the regulation of calcium-dependent pathways and endoplasmic reticulum stress. Our hypothesis is that additional mechanisms are involved in aortic aneurysm and atherosclerosis induced by SERCA2 dysfunction from the perspective of ASMC phenotypic transformation.
Methods & Results: In SERCA2 dysfunctional mice and their control littermates, ASMCs were isolated to analyze protein expression and cell functions, and angiotensin II was infused into these mice that were backcrossed into LDL receptor deficient background to induce aortic aneurysm and atherosclerosis.
Curr Opin Nephrol Hypertens
March 2025
Nephrology Division, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
Purpose Of Review: This review highlights the latest findings regarding hypocitraturia in autosomal dominant polycystic kidney disease (ADPKD), from both experimental and clinical studies, exploring the underlying pathophysiology and potential therapeutic approach.
Recent Findings: Experimental studies have shown that the lodging of microcrystals in the tubules can trigger cyst formation and growth in polycystic kidney disease (PKD). ADPKD patients are prone to developing hypocitraturia in early stages, which could predispose to calcium microcrystal formation.
Nat Rev Mol Cell Biol
January 2025
MitoCare Center, Department of Pathology and Genomic Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
Activation of Ca channels in Ca stores in organelles and the plasma membrane generates cytoplasmic calcium ([Ca]) signals that control almost every aspect of cell function, including metabolism, vesicle fusion and contraction. Mitochondria have a high capacity for Ca uptake and chelation, alongside efficient Ca release mechanisms. Still, mitochondria do not store Ca in a prolonged manner under physiological conditions and lack the capacity to generate global [Ca] signals.
View Article and Find Full Text PDFThe Ca 3.2 isoform of T-type voltage-gated calcium channels plays a crucial role in regulating the excitability of nociceptive neurons; the endogenous molecules that modulate its activity, however, remain poorly understood. Here, we used serum proteomics and patch-clamp physiology to discover a novel peptide albumin (1-26) that facilitates channel gating by chelating trace metals that tonically inhibit Ca 3.
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