150 research outputs found
Characterization of Granulations of Calcium and Apatite in Serum as Pleomorphic Mineralo-Protein Complexes and as Precursors of Putative Nanobacteria
Calcium and apatite granulations are demonstrated here to form in both human and
fetal bovine serum in response to the simple addition of either calcium or
phosphate, or a combination of both. These granulations are shown to represent
precipitating complexes of protein and hydroxyapatite (HAP) that display marked
pleomorphism, appearing as round, laminated particles, spindles, and films.
These same complexes can be found in normal untreated serum, albeit at much
lower amounts, and appear to result from the progressive binding of serum
proteins with apatite until reaching saturation, upon which the mineralo-protein
complexes precipitate. Chemically and morphologically, these complexes are
virtually identical to the so-called nanobacteria (NB) implicated in numerous
diseases and considered unusual for their small size, pleomorphism, and the
presence of HAP. Like NB, serum granulations can seed particles upon transfer to
serum-free medium, and their main protein constituents include albumin,
complement components 3 and 4A, fetuin-A, and apolipoproteins A1 and B100, as
well as other calcium and apatite binding proteins found in the serum. However,
these serum mineralo-protein complexes are formed from the direct chemical
binding of inorganic and organic phases, bypassing the need for any biological
processes, including the long cultivation in cell culture conditions deemed
necessary for the demonstration of NB. Thus, these serum granulations may result
from physiologically inherent processes that become amplified with calcium
phosphate loading or when subjected to culturing in medium. They may be viewed
as simple mineralo-protein complexes formed from the deployment of
calcification-inhibitory pathways used by the body to cope with excess calcium
phosphate so as to prevent unwarranted calcification. Rather than representing
novel pathophysiological mechanisms or exotic lifeforms, these results indicate
that the entities described earlier as NB most likely originate from calcium and
apatite binding factors in the serum, presumably calcification inhibitors, that
upon saturation, form seeds for HAP deposition and growth. These calcium
granulations are similar to those found in organisms throughout nature and may
represent the products of more general calcium regulation pathways involved in
the control of calcium storage, retrieval, tissue deposition, and disposal
Similarity in calcium channel activity of annexin V and matrix vesicles in planar lipid bilayers.
Matrix vesicles (MVs), structures that accumulate Ca2+ during the initiation of mineral formation in growing bone, are rich in annexin V. When MVs are fused with planar phospholipid bilayers, a multiconductance Ca2+ channel is formed, with activity essentially identical to that observed when annexin V is delivered to the bilayer with phosphatidylserine liposomes. Ca2+ currents through this channel, from either MV or annexin V liposomes, are blocked by Zn2+, as is Ca2+ uptake by MV incubated in synthetic cartilage lymph. Blockage by Zn2+ was most effective when applied to the side containing the MV or liposomes. ATP and GTP differentially modulated the activity of this channel: ATP increased the amplitude of the current and the number of conductance states; GTP dramatically reduced the number of events and conductance states, leading to well-defined Ca2+ channel activity from either MV or the annexin V liposomes. In the distinctive effects of ATP, GTP, and Zn2+ on the Ca2+ channel activity observed in both the MV and the liposome systems, the common factor was the presence of annexin V. From this we conclude that Ca2+ entry into MV results from the presence of annexin V in these membrane-enclosed structures
- …