The Acid Test of Fluoride: How pH Modulates Toxicity

Background: It is not known why the ameloblasts responsible for dental enamel formation are uniquely sensitive to fluoride ($F^−$). Herein, we present a novel theory with supporting data to show that the low pH environment of maturating stage ameloblasts enhances their sensitivity to a given dose of $F^−$. Enamel formation is initiated in a neutral pH environment (secretory stage); however, the pH can fall to below 6.0 as most of the mineral precipitates (maturation stage). Low pH can facilitate entry of $F^−$ into cells. Here, we asked if $F^−$ was more toxic at low pH, as measured by increased cell stress and decreased cell function. Methodology/Principal Findings: Treatment of ameloblast-derived LS8 cells with $F^−$ at low pH reduced the threshold dose of $F^−$ required to phosphorylate stress-related proteins, PERK, eIF2α, JNK and c-jun. To assess protein secretion, LS8 cells were stably transduced with a secreted reporter, Gaussia luciferase, and secretion was quantified as a function of $F^−$ dose and pH. Luciferase secretion significantly decreased within 2 hr of $F^−$ treatment at low pH versus neutral pH, indicating increased functional toxicity. Rats given 100 ppm $F^−$ in their drinking water exhibited increased stress-mediated phosphorylation of eIF2α in maturation stage ameloblasts (pH<6.0) as compared to secretory stage ameloblasts (pH∼7.2). Intriguingly, $F^−$-treated rats demonstrated a striking decrease in transcripts expressed during the maturation stage of enamel development (Klk4 and Amtn). In contrast, the expression of secretory stage genes, AmelX, Ambn, Enam and Mmp20, was unaffected. Conclusions: The low pH environment of maturation stage ameloblasts facilitates the uptake of $F^−$, causing increased cell stress that compromises ameloblast function, resulting in dental fluorosis

SULFONOLIPIDS NOVEL IN PROCARYOTES ARE SIGNIFICANT CELLULAR COMPONENTS OF MANY GLIDING BACTERIA

At least two different sulfonolipids, of chemical structure not heretofore recognized to occur in procaryotes, have been isolated, characterized and shown to be present in several genera of non-fruiting gliding bacteria. One of the lipids, capnine, is 2-amino-3-hydroxy-isoheptadecane-1l-sulfonic acid. Capnine and N-acylcapnine (the acyl group(s) of which appear to be C-15, C-16, and C-17 3-hydroxy moieties in the one organism studied) constitute 10% to 20% of the lipids of Capnocytophaga, Cytophaga, Beggiatoa, Flexibacter, Vitreoscilla and Sporocytophaga, and up to 3% of the cell dry weight. These quantitatively significant cell components may represent an important chemotaxonomic marker of non-fruiting gliding bacteria, for they appear to be absent from the fruiting myxobacters thus far examined, as they are also from E. coli and other bacteria which are either nonmotile, or motile as a result of flagellar action. The prospect that they may be associated with, or responsible for, motility in non-fruiting, gliding bacteria is raised