To analyze the involvement of structured water (bound to macromolecules) in apoptosis-induced mitochondrial outer-membrane permeability, we compared the dynamics of water protons from nuclear magnetic resonance (NMR) data in apoptotic liver mitochondria with that of control mitochondria incubated in vitro with free Ca(2+) (opening of the permeability transition pore, PTP) or with Bax alpha. Our results demonstrate that water molecules in apoptotic mitochondria exhibit an accelerated translational motion of structured water common with that induced by the opening of the PTP, but limited in amplitude. On the other hand, no significant quantitative change in structured water was observed in apoptotic mitochondria, a phenomenon also observed with Bax alpha-induced permeability. We conclude that the changes observed in the different water phases differ both quantitatively and qualitatively during the opening of the PTP and the Bax alpha-induced permeability, and that the apoptotic mitochondria exhibit mixed properties between these model situations.
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http://dx.doi.org/10.1038/sj.cdd.4401731 | DOI Listing |
Programmed cell death (apoptosis) is essential part of the process of tissue regeneration that also plays role in the mechanism of pathology. The phenomenon of fast and transient permeability of mitochondrial membranes by various triggers, known as permeability transition pore (mPTP) leads to the release of proapoptotic proteins and acts as an initial step in initiation of apoptosis. However, a role for mPTP was also suggested for physiology and it is unclear if there is a threshold in number of mitochondria with mPTP which induces cell death and how this mechanism is regulated in different tissues.
View Article and Find Full Text PDFEur J Med Chem
February 2025
Department of Medicinal Chemistry and Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Guangxi Normal University, Guilin, 541004, China. Electronic address:
As a central nervous system-specific member of the protein tyrosine phosphatase (PTP) family, the striatal-enriched protein tyrosine phosphatase (STEP) is an attractive drug target for neurodegenerative diseases. Here, we reported the discovery of a series of benzoic acid derivatives as new STEP inhibitors. Among them, compound 14b exhibited good STEP inhibitory activity and displayed selectivity against other PTPs.
View Article and Find Full Text PDFInt J Cardiol Heart Vasc
June 2024
Leiden University Medical Center, Department of Cardiology, The Netherlands.
Background And Aims: Currently applied methods for risk-assessment in coronary artery disease (CAD) often overestimate patients' risk for obstructive CAD. To enhance risk estimation, assessment of coronary artery calcium (CAC) can be applied. In 10 % of patients presenting with stable chest pain a previous non-gated computed tomography (CT) has been performed, suitable for CAC-assessment.
View Article and Find Full Text PDFXi Bao Yu Fen Zi Mian Yi Xue Za Zhi
March 2024
Department of Immunology of Basic Medical College, Binzhou Medical University, Yantai 264000, China. *Corresponding author, E-mail:
Objective To investigate the role of human leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) in the regulation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) and phosphatidylinositol 3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT /mTOR) signaling pathways in human acute myeloid leukemia HEL cells carrying the JAK2 V617F mutation, along with its effects on cell proliferation and apoptosis. MethodsThe JAK2 V617F mutation was identified using reverse transcription PCR and gene sequencing. The protein phosphatase (PTP) recruited by LAIR-1 was determined through co-immunoprecipitation and Western blot analysis.
View Article and Find Full Text PDFAm J Cardiol
December 2023
Department of Cardiology, Leiden University Medical Center, The Netherlands.
Given current pretest probability (PTP) estimations tend to overestimate patients' risk for obstructive coronary artery disease, evaluation of patients' coronary artery calcium (CAC) is more precise. The value of CAC assessment with the Agatston score on cardiac computed tomography (CT) for risk estimation has been well indicated in patients with stable chest pain. CAC can be equally well assessed on routine non-gated chest CT, which is often available.
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