Boric acid inhibits embryonic histone deacetylases: A suggested mechanism to explain boric acid-related teratogenicity

An RbAp48-like gene regulates adult stem cells in planarians

“…The nuclei were collected by centrifugation through 4 ml of cold sucrose cushion (30% sucrose, 10 mM Tris-HCl, pH 7.5, 10 mM NaCl, 3 mM MgCl 2 ) at 1300 g for 10 minutes at 4°C, resuspended in 400 l 10 mM Tris-HCl, pH 7.4, 10 mM NaCl, and centrifuged at 1300 g for 10 minutes at 4°C. Nuclear pellets were resuspended in 50 ml 1.5ϫ RIPA buffer (80 mM Tris-HCl, pH 7.5, 800 mM NaCl, 0.4% deoxycholic acid, 1.6% NP-40, 1.6 mM EDTA), incubated on ice for 30 minutes, and centrifuged at 10,000 g for 10 minutes at 4°C (modified from Di Renzo et al, 2007). The supernatant, containing nuclear proteins, was stored in aliquots at -80°C until use.…”

Role of Hog1, Tps1 and Sod1 in boric acid tolerance of Saccharomyces cerevisiae

“…Several different classes of enzymes have been identified as being sensitive to BA Bone et al, 1987;Di Renzo et al, 2007) and a first genome-wide analysis of BA sensitivity in yeast has been reported recently (Uluisik et al, 2011a). However, while being designed as a comprehensive study, the recently published genome-wide screening did not confirm either previously known BA resistance factors such as ATR1 and BOR1 (Kaya et al, 2009;Nozawa et al, 2006) or that other common stress response genes contribute to BA tolerance in S. cerevisiae.…”

“…Early in vitro studies have shown that BA is able to form complexes with cis-hydroxyl groups on carbohydrates, particularly on nucleotide cofactors -a property that may explain its inhibitory effect on oxidoreductases Kim et al, 2004). Subsequent studies have demonstrated inhibition of diverse other classes of enzymes, such as serine proteases and histone deacetylases (Bone et al, 1987;Di Renzo et al, 2007). At a cellular level, the molecular effects of BA lead to an inhibition of protein synthesis, the activation of MAP kinase cascades, an inhibition of cell cycle progression and morphological changes that add up to significant antiproliferative action on certain cancer cell lines (Uluisik et al 2011b;Barranco & Eckhert, 2006).…”

Pharmacological safety during pregnancy: the principles of teratogenesis and teratogenicity of drugs

“…В литературе отсутствуют работы об эффектах ингибирования гистондеацетила-зы в патогенезе врожденных аномалий у человека. Однако, экспериментальные исследования свидетель-ствуют о развитии мальформаций осевого скелета [70,71] и нервной трубки [72]. Препараты, ингибирую-щие гистондеацетилазы, включают вальпроевую кис-лоту [73], противогрибковый антибиотик трихостатин A [74] и салицилаты [75].…”

“…Препараты, ингибирую-щие гистондеацетилазы, включают вальпроевую кис-лоту [73], противогрибковый антибиотик трихостатин A [74] и салицилаты [75]. Кроме того, борная кислота как неактивный ингредиент, используемый в лекарствен-ных препаратах, а также в качестве отпускаемого без рецепта антибактериального продукта, может вызы-вать гиперацетилирование гистонов на уровне сомитов эмбриона [71].…”