apyrase has been researched along with diphosphoric-acid* in 2 studies
2 other study(ies) available for apyrase and diphosphoric-acid
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ATP-based therapy prevents vascular calcification and extends longevity in a mouse model of Hutchinson-Gilford progeria syndrome.
Pyrophosphate deficiency may explain the excessive vascular calcification found in children with Hutchinson-Gilford progeria syndrome (HGPS) and in a mouse model of this disease. The present study found that hydrolysis products of ATP resulted in a <9% yield of pyrophosphate in wild-type blood and aortas, showing that eNTPD activity (ATP → phosphate) was greater than eNPP activity (ATP → pyrophosphate). Moreover, pyrophosphate synthesis from ATP was reduced and pyrophosphate hydrolysis (via TNAP; pyrophosphate → phosphate) was increased in both aortas and blood obtained from mice with HGPS. The reduced production of pyrophosphate, together with the reduction in plasma ATP, resulted in marked reduction of plasma pyrophosphate. The combination of TNAP inhibitor levamisole and eNTPD inhibitor ARL67156 increased the synthesis and reduced the degradation of pyrophosphate in aortas and blood ex vivo, suggesting that these combined inhibitors could represent a therapeutic approach for this devastating progeroid syndrome. Treatment with ATP prevented vascular calcification in HGPS mice but did not extend longevity. By contrast, combined treatment with ATP, levamisole, and ARL67156 prevented vascular calcification and extended longevity by 12% in HGPS mice. These findings suggest a therapeutic approach for children with HGPS. Topics: Adenosine Triphosphate; Alkaline Phosphatase; Animals; Antigens, CD; Aortic Diseases; Apyrase; Calcinosis; Diphosphates; Disease Models, Animal; Gene Knock-In Techniques; Humans; Lamin Type A; Levamisole; Longevity; Male; Mice; Mice, Transgenic; Myocytes, Smooth Muscle; Phosphoric Diester Hydrolases; Progeria; Pyrophosphatases; Real-Time Polymerase Chain Reaction; RNA Interference; RNA, Small Interfering | 2019 |
Synthesis of Extracellular Pyrophosphate Increases in Vascular Smooth Muscle Cells During Phosphate-Induced Calcification.
Objective- Hydroxyapatite deposition on the medial layer of the aortic walls is the hallmark of vascular calcification and the most common complication in aging individuals and in patients with diabetes mellitus and those undergoing hemodialysis. Extracellular pyrophosphate is a potent physicochemical inhibitor of hydroxyapatite crystal formation. This study analyzed changes in extracellular pyrophosphate metabolism during the phosphate-induced calcification process. Approach and Results- Phosphate-induced calcification of ex vivo-cultured aortic rings resulted in calcium accumulation after 7 days. This accumulation was enhanced when aortic walls were devitalized. BMP2 (bone morphogenic protein 2) expression was associated with calcium accumulation in cultured aortic rings, as well as in cultured vascular smooth muscle cells (VSMCs) and in calcitriol-induced calcification in rats. Hydroxyapatite dose dependently induced BMP2 overexpression in VSMCs. Moreover, TNAP (tissue nonspecific alkaline phosphatase) mRNA levels and activity were found to be downregulated in early phases and upregulated in later phases of calcification in all 3 models studied. eNPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) increased from early to later phases of calcification, whereas eNTPD1 (ectonucleoside triphosphate diphosphohydrolase 1) was downregulated during later phases. Synthesis of pyrophosphate in VSMCs increased significantly over time, in all 3 models studied. Because the rate of pyrophosphate hydrolysis was 10× slower than the rate of pyrophosphate synthesis, pyrophosphate synthesis is determined mainly by the ratio of eNPP1 to eNTPD1 activity. Hydroxyapatite also induces increments both in TNAP and eNPP1/eNTPD1 ratio in VSMCs. Conclusions- Pyrophosphate synthesis increases in VSMCs during phosphate-induced calcification because of compensatory regulation of extracellular pyrophosphate metabolism. Topics: Alkaline Phosphatase; Animals; Antigens, CD; Aorta; Apyrase; Bone Morphogenetic Protein 2; Cell Proliferation; Cells, Cultured; Diphosphates; Down-Regulation; Durapatite; Extracellular Space; Gene Expression; Hydrolysis; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Phosphates; Phosphoric Diester Hydrolases; Pyrophosphatases; Rats, Sprague-Dawley; RNA, Messenger; Up-Regulation; Vascular Calcification | 2018 |