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Estimation of the Mechanism of Adrenal Action of Endocrine-Disrupting Compounds Using a Computational Model of Adrenal Steroidogenesis in NCI-H295R Cells
المؤلفون المشاركون
Saito, Ryuta
Terasaki, Natsuko
Yamazaki, Makoto
Masutomi, Naoya
Tsutsui, Naohisa
Okamoto, Masahiro
المصدر
العدد
المجلد 2016، العدد 2016 (31 ديسمبر/كانون الأول 2016)، ص ص. 1-19، 19ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2016-02-17
دولة النشر
مصر
عدد الصفحات
19
التخصصات الرئيسية
الملخص EN
Adrenal toxicity is one of the major concerns in drug development.
To quantitatively understand the effect of endocrine-active compounds on adrenal steroidogenesis and to assess the human adrenal toxicity of novel pharmaceutical drugs, we developed a mathematical model of steroidogenesis in human adrenocortical carcinoma NCI-H295R cells.
The model includes cellular proliferation, intracellular cholesterol translocation, diffusional transport of steroids, and metabolic pathways of adrenal steroidogenesis, which serially involve steroidogenic proteins and enzymes such as StAR, CYP11A1, CYP17A1, HSD3B2, CYP21A2, CYP11B1, CYP11B2, HSD17B3, and CYP19A1.
It was reconstructed in an experimental dynamics of cholesterol and 14 steroids from an in vitro steroidogenesis assay using NCI-H295R cells.
Results of dynamic sensitivity analysis suggested that HSD3B2 plays the most important role in the metabolic balance of adrenal steroidogenesis.
Based on differential metabolic profiling of 12 steroid hormones and 11 adrenal toxic compounds, we could estimate which steroidogenic enzymes were affected in this mathematical model.
In terms of adrenal steroidogenic inhibitors, the predicted action sites were approximately matched to reported target enzymes.
Thus, our computer-aided system based on systems biological approach may be useful to understand the mechanism of action of endocrine-active compounds and to assess the human adrenal toxicity of novel pharmaceutical drugs.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Saito, Ryuta& Terasaki, Natsuko& Yamazaki, Makoto& Masutomi, Naoya& Tsutsui, Naohisa& Okamoto, Masahiro. 2016. Estimation of the Mechanism of Adrenal Action of Endocrine-Disrupting Compounds Using a Computational Model of Adrenal Steroidogenesis in NCI-H295R Cells. Journal of Toxicology،Vol. 2016, no. 2016, pp.1-19.
https://search.emarefa.net/detail/BIM-1110821
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Saito, Ryuta…[et al.]. Estimation of the Mechanism of Adrenal Action of Endocrine-Disrupting Compounds Using a Computational Model of Adrenal Steroidogenesis in NCI-H295R Cells. Journal of Toxicology No. 2016 (2016), pp.1-19.
https://search.emarefa.net/detail/BIM-1110821
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Saito, Ryuta& Terasaki, Natsuko& Yamazaki, Makoto& Masutomi, Naoya& Tsutsui, Naohisa& Okamoto, Masahiro. Estimation of the Mechanism of Adrenal Action of Endocrine-Disrupting Compounds Using a Computational Model of Adrenal Steroidogenesis in NCI-H295R Cells. Journal of Toxicology. 2016. Vol. 2016, no. 2016, pp.1-19.
https://search.emarefa.net/detail/BIM-1110821
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1110821
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
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تقوم هذه الخدمة بالتحقق من التشابه أو الانتحال في الأبحاث والمقالات العلمية والأطروحات الجامعية والكتب والأبحاث باللغة العربية، وتحديد درجة التشابه أو أصالة الأعمال البحثية وحماية ملكيتها الفكرية. تعرف اكثر
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