Connective tissue mineralization in Abcc6−/− mice, a model for pseudoxanthoma elasticum

Abstract

Pseudoxanthoma elasticum (PXE) is a heritable multisystem disorder characterized by ectopic mineralization. However, the structure of the mineral deposits, their interactions with the connective tissue matrix, and the details of the progressive maturation of the mineral crystals are currently unknown. In this study, we examined the mineralization processes in Abcc6−/− mice, a model system for PXE, by energy dispersive X-ray, and Fourier transform infrared imaging spectroscopy (FT-IRIS). The results indicated that the principal components of the mineral deposits were calcium and phosphate which co-localized within the histologically demonstrable lesions determined by topographic mapping. The Ca/P ratio increased in samples with progressive mineralization reaching the value comparable to that in endochondral bone. A progressive increase in mineralization was also reflected by increased mineral-to-matrix ratio determined by FT-IRIS. Determination of the mineral phases by FT-IRIS suggested progressive maturation of the mineral deposits from amorphous calcium phosphate to hydroxyapatite. These results provide critical information of the mechanisms of mineralization in PXE, with potential pharmacologic implications.

Expression pattern of the human ABC transporters in pluripotent embryonic stem cells and in their derivatives

“…Since the ABCC1 and ABCA1 antibodies recognize intracellular epitopes, the increased protein levels found in the permeabilized cells most probably correspond to increased general expression levels, and in this case the plasma membrane or intracellular membrane expression levels cannot be distinguished. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 protein, as this transporter has been indicated to play an important role in cardiac tissues (17,18). However, we could not detect ABCC6 expression in any of the examined hESCderived cell types.…”

Mechanisms of Oxidative Stress an d Vessels Sclerotic Transformation Initiated by Uremic Toxin Indoxyl Sulfate

“…Confirmation of this can be data [32], which noted the presence of certain amounts of Ca and Mg carbonates in products of tissue mineralization. Clearly that a formation of calcium phosphate or calcium carbonate cross-linking of the proteins of polypeptide chains under oxidative stress conditions will depend on the ratio of HPO 4 2ˉ and CO 3 2ˉ anions in biological fluids.…”

“…In fact, namely thiol groups provide antioxidant protection of tissues, and therefore ROS have to react with them primarily in the oxidative stress conditions. The evidences about possibility of such processes are shown in [32], where was studied the oxidative conversion of thiol groups of albumin into corresponding sulfur-containing acidic groups. The obtained in this case oxidized albumin can be considered, in our opinion, as a protein, that in some way simulate the transformations of polypeptides in tissues in oxidative stress conditions.…”

“…The obtained in this case oxidized albumin can be considered, in our opinion, as a protein, that in some way simulate the transformations of polypeptides in tissues in oxidative stress conditions. It is well known that polypeptide fragments of proteins, in particularly bind by disulfide bonds -S-S-which may also can be oxidized in sulfonic groups [32]. This means that an additional source of sulfonic groups in proteins under oxidative stress conditions also can be oxidized -S-S-groups.…”

“…As for the possible presence of anionic centers of R-Oˉ in adjacent fragments of polypeptides, the anionic oxygen can be not only in the sulfonic, but also in others, most likely in carboxyl groups, which also have the increased affinity to Ca 2+ ions. This is possible, if we take into account the data [32], according to which the molecule of native albumin (a model protein) at pH 7.4 has ~ 19 negative charges in polypeptide chains. It seems that fragments with type (11) and (12) occurring in oxidative stress conditions on the intravascular surface of vascular proteins may also play role as formation centers for calcium sclerotic plaques, because the presence of anions (R 1 -Oˉ) and cations (R 2 -Ca + ) groups in these mineral fragments opens also the way to three-dimensional growth of these mineral-organic formations.…”