Adenosine triphosphate (ATP) is one of the most important nucleotides. Found in all known life forms, it is often called the "molecular unit of currency" of intracellular energy transfer. It provides energy to drive and support many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. In recent years, and collaboration with different research groups (Brazil, France, Japan, Italy) we have started a deep interest in the analysis of extracellular ATP to monitor such diseases where the degradation of this nucleotide is the substrate for the tissue non-specific alkaline phosphatase (TNAP), suspected to induce atherosclerosis plaque calcification. TNAP, during physiological mineralization, hydrolyzes the mineralization inhibitor inorganic pyrophosphate (PPi). Since atherosclerosis plaques are characterized by the presence of necrotic cells that probably release supraphysiological concentrations of ATP, we explored whether this extracellular ATP is hydrolyzed into the mineralization inhibitor PPi or the mineralization stimulator inorganic phosphate (Pi), and whether TNAP is involved. Degradation of ATP and mineralization by tissue-nonspecific alkaline phosphatase (TNAP), Na,K,-ATPase (NKA) could be involved in supplying phosphate (Pi) in the early stages of Matrix Vesicles-mediated mineralization. Thus, we have studied with different chemical-physical techniques the degradation of APT in forming PPi: 31P NMR, IR. Our findings suggest that high ATP levels released by cells near vascular smooth muscle cells (VSMCs) in atherosclerosis plaques generate Pi and not PPi, which may exacerbate plaque calcification.
22 Marzo, 2024 - ore 14:00
Prof. Michele Fiore, Maitre de Conference, Université de Lyon, Claude Bernard Lyon 1, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Villeurbanne, France
michele.fiore@univ-lyon1.fr