A quantitative in vivo assay for craniofacial developmental toxicity of histone deacetylases

نویسندگان

چکیده

Many bony features of the face develop from endochondral ossification preexisting collagen-rich cartilage structures. The proper development these structures is essential to morphological formation face. developmental programs governing pre-bone facial cartilages are sensitive chemical compounds that disturb histone acetylation patterns and chromatin structure. We have taken advantage this fact a quantitative assay craniofacial toxicity based on distortion deterioration in zebrafish larvae upon exposure increasing concentrations several well-described deacetylase inhibitors. In assay, we measure angle formed by developing ceratohyal bone as precise, proxy for overall status cartilages. Using well-established toxicant deacetylase-inhibiting compound valproic acid along with 12 structurally related compounds, demonstrate applicability investigate structure-activity relationships.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Interaction of histone acetylases and deacetylases in vivo.

Having opposing enzymatic activities, histone acetylases (HATs) and deacetylases affect chromatin and regulate transcription. The activities of the two enzymes are thought to be balanced in the cell by an unknown mechanism that may involve their direct interaction. Using fluorescence resonance energy transfer analysis, we demonstrated that the acetylase PCAF and histone deacetylase 1 (HDAC1) ar...

متن کامل

diagnostic and developmental potentials of dynamic assessment for writing skill

این پایان نامه بدنبال بررسی کاربرد ارزیابی مستمر در یک محیط یادگیری زبان دوم از طریق طرح چهار سوال تحقیق زیر بود: (1) درک توانایی های فراگیران زمانیکه که از طریق برآورد عملکرد مستقل آنها امکان پذیر نباشد اما در طول جلسات ارزیابی مستمر مشخص شوند; (2) امکان تقویت توانایی های فراگیران از طریق ارزیابی مستمر; (3) سودمندی ارزیابی مستمر در هدایت آموزش فردی به سمتی که به منطقه ی تقریبی رشد افراد حساس ا...

15 صفحه اول

Chemical Phylogenetics of Histone Deacetylases

The broad study of histone deacetylases in chemistry, biology and medicine relies on tool compounds to derive mechanistic insights. A phylogenetic analysis of class I and II histone deacetylases (HDACs) as targets of a comprehensive, structurally diverse panel of inhibitors revealed unexpected isoform selectivity even among compounds widely perceived as nonselective. The synthesis and study of ...

متن کامل

Quantitative in vitro to in vivo extrapolation of cell-based toxicity assay results.

The field of toxicology is currently undergoing a global paradigm shift to use of in vitro approaches for assessing the risks of chemicals and drugs in a more mechanistic and high throughput manner than current approaches relying primarily on in vivo testing. However, reliance on in vitro data entails a number of new challenges associated with translating the in vitro results to corresponding i...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

ژورنال

عنوان ژورنال: Toxicology Letters

سال: 2021

ISSN: ['0378-4274', '1879-3169']

DOI: https://doi.org/10.1016/j.toxlet.2021.02.005