The cadmium effects described below are largely identical to those observed in the literature on the molecular actions of fluoride.
See also: Dental Fluorosis = Dental Cadmiosis
Misra UK, Gawdi G, Pizzo SV - "Induction of mitogenic signalling in the 1LN
prostate cell line on exposure to submicromolar concentrations of cadmium+" Cell
Signal 15(11):1059-70 (2003)
Cadmium exposure increases the risk of prostate cancer. We now describe the
effects of Cd2+ on signalling and proliferation in 1LN prostate cells. Cd2+
increased [3H]thymidine uptake and cell number twofold. Cd2+ elevated
intracellular IP3, cytosolic-free Ca2+, phosphorylated MEK1/2, ERK1/2, p38 MAPK
and JNK two- to threefold. Increased PDK1 and phosphorylation of the 85-kDa
regulatory subunit of PI 3-kinase, Akt and p70s6k were also observed. Cd2+
treatment increased transcription factors NFkappaB and CREB, and the expression
of c-fos and c-myc. Cd2+-induced increased uptake of [3H]thymidine was abolished
by translational and transcriptional inhibitors, and Ca2+ channel blockers.
Inhibition of phospholipase C and of Ca2+ binding to IP3 receptors inhibited
Cd2+-induced DNA synthesis as did inhibition of tyrosine kinases, protein kinase
C, PI 3-kinase, farnesyl transferase, MEK1/2, ERK1/2 and p38MAPK. Thus signalling
events, which are triggered on exposure of 1LN cells to submicromolar
concentrations of Cd2+, induce increased proliferation of these cells.
Kakei M, Sakae T, Yoshikawa M -" Mechanism of cadmium induced crystal defects in
developing rat tooth enamel" Proc Jpn Acad Ser B Phys Biol Sci.
It is well known that exposure to environmental cadmium causes itai-itai
(ouch-ouch) disease. However, the exact mechanism underlying this bone disease
remains unresolved. By focusing on the calcification mechanism, we examined
developing tooth enamel in rats exposed to cadmium to test the hypothesis that
cadmium exposure may cause defects in crystal formation. Electron microscopy
revealed the presence of perforated crystals in developing tooth enamel,
indicating that the process of crystal nucleation may have been interrupted by
cadmium exposure. Furthermore, biochemical analyses revealed that the catalytic
activity of carbonic anhydrase in the immature enamel matrix declined remarkably
despite the fact that quantitative reduction of this enzyme was insignificant,
suggesting that the decline of catalytic activity may have resulted from the
replacement of zinc with cadmium ions. Therefore, we concluded that the poor
catalytic activity of cadmium-binding carbonic anhydrase might hinder the
nucleation process, leading to an impairment in mineralization that causes
Wöltgens JH, Lyaruu DM, Bervoets TJ -" Possible functions of alkaline
phosphatase in dental mineralization: cadmium effects" J Biol Buccale
In mineralizing dental tissues the non-specific alkaline phosphatase, using
paranitrophenylphosphate (p-NPP) as substrate, is also capable of splitting
inorganic pyrophosphate (PPi). In contrast to the p-NPP-ase part of the enzyme,
the PPi-ase part requires Zn2+ as a cofactor for its hydrolytic activity. The
PPi-ase activity of the enzyme can be inhibited by cadmium ions (Cd2+), perhaps
by replacing Zn2+ from the active site of the enzyme molecule. In addition to
splitting PPi, the PPi-ase part of the enzyme may also be involved in the
phosphorylation process of yet undetermined organic macromolecules. Cd2+ inhibits
this phosphorylation process. Inhibition of the PPi-ase activity can also be
accomplished by ascorbic acid known for its capacity to complex bivalent cations.
Ascorbic acid may accordingly also remove Zn2+ from the active site of the
PPi-ase. It is suggested that in developing dental tissues alkaline phosphatase
is not only associated with the transport of phosphate ions towards the
mineralization front, but is also involved in the phosphorylation of organic
macromolecules, a process activated the PPi-ase part of the enzyme.
Mottled teeth just like "fluorosis"...
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