Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Matrix vesicles (MVs) are extracellular, 100 nM in diameter, membrane-invested particles selectively located at sites of initial calcification in cartilage, bone, and predentin. The first crystals of apatitic bone mineral are formed within MVs close to the inner surfaces of their investing membranes. Matrix vesicle biogenesis occurs by polarized budding and pinching-off of vesicles from specific regions of the outer plasma membranes of differentiating growth plate chondrocytes, osteoblasts, and odontoblasts. Polarized release of MVs into selected areas of developing matrix determines the nonrandom distribution of calcification. Initiation of the first mineral crystals, within MVs (phase 1), is augmented by the activity of MV phosphatases (eg, alkaline phosphatase, adenosine triphosphatase and pyrophosphatase) plus calcium-binding molecules (eg, annexin I and phosphatidyl serine), all of which are concentrated in or near the MV membrane. Phase 2 of biologic mineralization begins with crystal release through the MV membrane, exposing preformed hydroxyapatite crystals to the extracellular fluid. The extracellular fluid normally contains sufficient Ca2+ and PO4(3-) to support continuous crystal proliferation, with preformed crystals serving as nuclei (templates) for the formation of new crystals by a process of homologous nucleation. In diseases such as osteoarthritis, crystal deposition arthritis, and atherosclerosis, MVs initiate pathologic calcification, which, in turn, augments disease progression.
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PMID:Matrix vesicles and calcification. 1274 15

Membrane-bound extracellular matrix vesicles play an important role in the de novo initiation and propagation of calcium-phosphate mineral formation in calcifying cartilage, bone, dentin, and in pathologic calcification. Characterization of the phase, composition, crystal size, and perfection provides valuable insight into the mechanism of the mineral deposition. In the present study, Fourier transform infrared imaging spectroscopy (FT-IRIS) was used to characterize the mineral phase generated during MV-mediated in vitro mineralization. FT-IRIS studies revealed that the mineral phase associated with MVs calcified in the presence of AMP and beta-GP was always found to be crystalline hydroxyapatite while with ATP only a small amount of immature mineral, most likely an amorphous or poorly crystalline hydroxyapatite, was observed. Low concentrations of pyrophosphate (PPi) (< or = 0.01 mM) showed apatitic mineral while high concentrations showed immature calcium pyrophosphate dihydrate (CPPD). The implications of these findings are that (a) hydrolysis of AMP or beta-GP, monophosphoester substrates of MV-5' AMPase (substrate: AMP) and TNAP (substrates: AMP, beta-GP), yields orthophosphate (Pi) which leads to the formation of mature crystalline, apatite mineral, while the hydrolysis of ATP, substrate for MV-TNAP or ATPase or NPP1, inhibits the formation of mature hydroxyapatite, and (b) pyrophosphate (PPi) has a bimodal effect on mineralization, i.e., at low PPi concentrations, alkaline phosphatase activity of matrix vesicles is able to hydrolyze PPi to orthophosphate and thus facilitates the formation of basic calcium phosphate mineral which subsequently transforms into apatitic mineral. We hypothesize that, at high PPi concentrations, PPi by itself or Pi released by partial PPi hydrolysis could act as inhibitors of alkaline phosphatase activity, thereby preventing complete hydrolysis of PPi to Pi, and thus resulting in the accumulation of calcium pyrophosphate dihydrate. Therefore, in order for physiological mineralization to proceed, a balance is required between levels of Pi and PPi.
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PMID:Nature of phosphate substrate as a major determinant of mineral type formed in matrix vesicle-mediated in vitro mineralization: An FTIR imaging study. 1646 Oct 32

Erythrocyte-derived depressing factor (EDDF) shows significant protective effects on blood vessels from hypertensive rats, by regulating vascular reactivity, calcium homeostasis, DNA synthesis, and cell cycle progression in vascular smooth muscles (VSMCs). Arteries from hypertensive and aging people have high levels of accumulated calcium. However, in the life span of experimental animals commonly used, arterial calcium content does not reach cytotoxic levels observed in human. An overdose of vitamin D(3) results in a rapid arterial calcium overload. Using rats with arterial calcinosis and age- and gender-matched Wistar controls, we investigated whether EDDF has beneficial effect on blood vessels from animals with arterial calcinosis. Blood vessel functions were impaired in rats with arterial calcinosis, as indicated by decreased Ca(2+)-ATPase activity, increased vasoconstrictor responses to alpha1 adrenoceptor agonist phenylephrine and increased ERK1/2 phosphorylation. Arterial calcium overload also impaired the morphological integrity of VSMCs. EDDF restored the abovementioned abnormalities caused by arterial calcinosis, and inhibited cell cycle progression of VSMCs induced by angiotensin II. In conclusion, EDDF may protect blood vessels from animals with arterial calcinosis, which is mediated by regulating calcium homeostasis, vascular reactivity and cell cycle progression as well as by improving morphological integrity of VSMCs.
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PMID:Experimental vasoprotection by a novel erythrocyte-derived depressing factor in rats with arterial calcinosis. 1899 68