{"id":859,"date":"2019-08-20T22:40:24","date_gmt":"2019-08-20T22:40:24","guid":{"rendered":"http:\/\/chooselife.co.uk\/?p=859"},"modified":"2019-08-20T22:40:24","modified_gmt":"2019-08-20T22:40:24","slug":"the-acid-test-of-fluoride-how-ph-modulates-toxicity","status":"publish","type":"post","link":"https:\/\/chooselife.co.uk\/index.php\/2019\/08\/20\/the-acid-test-of-fluoride-how-ph-modulates-toxicity\/","title":{"rendered":"The Acid Test of Fluoride: How pH Modulates Toxicity"},"content":{"rendered":"\n

Abstract<\/strong><\/h2>\n\n\n\n

Background<\/h3>\n\n\n\n

It is not known why the ameloblasts responsible for dental enamel formation are uniquely sensitive to fluoride (F\u2212<\/sup>). 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\u2212<\/sup>. 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\u2212<\/sup> into cells. Here, we asked if F\u2212<\/sup> was more toxic at low pH, as measured by increased cell stress and decreased cell function.<\/p>\n\n\n\n

Methodology\/Principal Findings<\/h3>\n\n\n\n

Treatment of ameloblast-derived LS8 cells with F\u2212<\/sup> at low pH reduced the threshold dose of F\u2212<\/sup>required to phosphorylate stress-related proteins, PERK, eIF2\u03b1, JNK and c-jun. To assess protein secretion, LS8 cells were stably transduced with a secreted reporter, Gaussia luciferase<\/em>, and secretion was quantified as a function of F\u2212<\/sup> dose and pH. Luciferase secretion significantly decreased within 2 hr of F\u2212<\/sup> treatment at low pH versus neutral pH, indicating increased functional toxicity. Rats given 100 ppm F\u2212<\/sup> in their drinking water exhibited increased stress-mediated phosphorylation of eIF2\u03b1 in maturation stage ameloblasts (pH<6.0) as compared to secretory stage ameloblasts (pH\u223c7.2). Intriguingly, F\u2212<\/sup>-treated rats demonstrated a striking decrease in transcripts expressed during the maturation stage of enamel development (Klk4<\/em> and Amtn<\/em>). In contrast, the expression of secretory stage genes, AmelX<\/em>, Ambn<\/em>, Enam<\/em>and Mmp20<\/em>, was unaffected.<\/p>\n\n\n\n

Conclusions<\/h3>\n\n\n\n

The low pH environment of maturation stage ameloblasts facilitates the uptake of F<\/strong>\u2212<\/strong><\/sup>, causing increased cell stress that compromises ameloblast function, resulting in dental fluorosis.<\/strong><\/p>\n\n\n\n

Full : https:\/\/journals.plos.org\/plosone\/article?id=10.1371\/journal.pone.0010895<\/a> <\/p>\n\n\n\n

<\/p>\n","protected":false},"excerpt":{"rendered":"

Abstract Background It is not known why the ameloblasts responsible for dental enamel formation are uniquely sensitive to fluoride (F\u2212). 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\u2212. Enamel formation is initiated in a … <\/p>\n

Continue reading “The Acid Test of Fluoride: How pH Modulates Toxicity”<\/span><\/a><\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[],"class_list":["post-859","post","type-post","status-publish","format-standard","hentry","category-ph"],"_links":{"self":[{"href":"https:\/\/chooselife.co.uk\/index.php\/wp-json\/wp\/v2\/posts\/859","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/chooselife.co.uk\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/chooselife.co.uk\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/chooselife.co.uk\/index.php\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/chooselife.co.uk\/index.php\/wp-json\/wp\/v2\/comments?post=859"}],"version-history":[{"count":1,"href":"https:\/\/chooselife.co.uk\/index.php\/wp-json\/wp\/v2\/posts\/859\/revisions"}],"predecessor-version":[{"id":860,"href":"https:\/\/chooselife.co.uk\/index.php\/wp-json\/wp\/v2\/posts\/859\/revisions\/860"}],"wp:attachment":[{"href":"https:\/\/chooselife.co.uk\/index.php\/wp-json\/wp\/v2\/media?parent=859"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/chooselife.co.uk\/index.php\/wp-json\/wp\/v2\/categories?post=859"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/chooselife.co.uk\/index.php\/wp-json\/wp\/v2\/tags?post=859"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}