Регуляция активности цитохромов Р450 химическими и физическими факторами
Механизмы иидукцин CYP1A1 и CYP1A2 а-токоферолом. Изменения активности CYP1A1 и CYP1A2 в ответ на введение а-токоферола имеют различные времяи дозо-зависимые закономерности, что свидетельствует о комплексности механизмов регуляции, лежащих в их основе. Картина регуляции активности CYP1A1 и IA2 а-токоферолом оказалась сложной. Анализ времяи дозо-зависимых закономерностей увеличения относительного… Читать ещё >
Содержание
- СПИСОК СОКРАЩЕНИЙ
- ГЛАВА 1. ОБЗОР ЛИТЕРАТУРЫ
- 1. 1. Ферменты моноокснгеназпой системы
- 1. 1. 1. Суоерсемейство цктохромов Р
- 1. 1. 1. 1. Индукция цнтохромов Р450 ксенобиотиками 1 б
- 1. 1. 1. 2. Подсемейство CYP1А
- 1. 2. 1. 3. Подсемейство CYP2A
- 1. 1. 1. 4. Подсемейство СYP2B
- 1. 2. 1. 5. Подсемейство CYP2C
- 1. 2. 1. 6. Подсемейство CYP3A
- 1. 2. 2. НАДФН-цитохром Р450 редуктаза
- 1. 1. 1. Суоерсемейство цктохромов Р
- 1. 2. Механизмы регуляции экспрессии цнтохромов P45Q
- 1. 2. 1. Регуляция генов CYP1A
- I. 2.1.1. Индукция CYP1А полициклическими ароматическими углеводородами
- II. 1.2. Некласснческие экзогенные индукторы CYP1А
- 1. 2. 1. 3. Эндогенные индукторы CYP 1А
- 1. 2. 1. 4. Негативная регуляция CYP 1А
- 1. 2. 2. Регуляция генов CYP2B
- 1. 2. 2. 1. Индукция экспрессии СУР2 В через дистальный промотор
- 1. 2. 2. 2. Участие проксимального промотора в индукции генов CYP2B 39 1.2.2.3 Другие регу ляториые элементы генов CYP2B
- 1. 2. 3. Регуляция генов CYP2C
- 1. 2. 4. Регуляция генов CYP2A
- 1. 3. 5. Регуляция генов CYP3A
- 1. 3. Химические соединения, влияние которых на моноокенгеназную систему печени исследовалось в настоящей работе
- 1. 3. 1. Полностью фторированное органическое соединение перфтордекалин
- 1. 3. 2. Пиридин и пиридин-И-оксид
- 1. 2. 1. 3. Эндогенные индукторы CYP 1А
- 1. 1. Ферменты моноокснгеназпой системы
- 3. Ннфеднпин
- 1. 3. 4. Витамин Е (а-токоферол)
- 1. 3. 5. Витамин К. функции в организме и влияние на цитохром Р
- 1. 3. 6. Кверцетии 60 13.7. Билирубин
- 1. 4. Физические факторы, влияние которых на монооксигеназиую систему печени исследовалось в настоящей работе
- 1. 5. 1. Лазерное излучение
- 1. 5. 2. Электромагнитные колебания сантиметрового диапазона
- 1. 5. 3. Ультразвук низкой интенсивности
- 1. 5. 4. Радиация
- 1. 5. 5. ХоиодовоК фактор
- 2. 1. Материалы
- 22. Животные
- 2. 2. 1. — Экспериментальные процедуры с животными
- 2. 3. Методы исследования
- 2. 3. 1. Выделение микросом из печени крыс
- 2. 3. 2. Определение количества белка в микросомах
- 2. 3. 3. Определение количества цитохромов Р
- 2. 3. 4. Определение активности НАДФН-цитохром Р450 редуктазы
- 2. 3. 5. Выделение и очистка CYP2B1 и CYP2B2 из микросом печени крыс, индуцированных фенобарбиталом
- 2. 3. 6. Выделение и очистка CYP1A1 и CYP1А2 из микросом печени крыс, индуцированных 3-метилхолантреном
- 2. 3. 7. Получение моноспецнфических поликлональных антител
- 2. 3. 8. Получение моноклональных антител
- 2. 3. 9. Иммунохимический анализ белков микросом
- 2. 3. 10. Определение активности CYP1A, CYP2A, CYP2B, CYP2C и CYP3A в микросомах печени крыс
- 2. 3. 11. Выделение суммарной РНК из клеток печени крыс
- 2. 3. 12. Электрофорез РНК в частично денатурирующих условиях
- 2. 3. 13. Определение концентрации и чистоты РНК 95 2−3.14. Определение относительного содержания мРНК CYP1A1, СУР1А2 95 2.3.15- Выделение экстракта ядер клеток печени
- 2. 3. 16. Определение белка в экстрактах ядер
- 2. 3. 17. Приготовление зонда для ДНК/белкового связывания
- 2. 3. 18. Анализ ДНК/белковых комплексов
2.3.19. Количественное определение малонового диальдегида 99 2.3.19. Определение токоферолов в микросомах печени крыс 99 2 3.20. Определение концентрации внеэрнтроцнтарного гемоглобина 100 2.3.21. Определение общего и коньюгированного билирубина
2.4. Статистическая обработка данных.
ГЛАВА 3. РЕЗУЛЬТАТЫ ИССЛЕДОВАНИЙ И ИХ ОБСУЖДЕНИЕ
3.1. Исследование влняния химических соединений на ферменты монооксигеназной системы печени
3.1.1. Влияние перфтордекалина на активности ферментов монооксигеназной
3.1.2. Влияние пиридина и пиридин-Ы-оксида ш монооксигеназной системы печени 10:
3.1.3. Влияние нифеднпина на активность ферментов монооксигеназной системы
3.1.4. Влияние а-токоферола на активность ферментов монооксигеназной системы печени 1К
3.1.5. Влияние менадиоиа на активность ферментов монооксигеназной системы
3.1.6. Влияние кверцетина на активность CYP1A в микросомах печени 1 Г
3.1.7. Влияние билирубина на активность CYPl А! в микросомах печени 11!
3.2. Исследование механизмов индукции активности CYP1A1 и CYP1A2 в печени крыс «некласснческнмн» нндукторамн
3.2,1. Молекулярные механизмы, лежащие в основе индукции активности CYP1А а-токоферолом
3−2.2. Молекулярные механизмы, лежащие в основе индукции активности CYPIA менадионом
3.2.3. Молекулярный механизм, лежащий в основе индукции активности CYP1AI билирубином
3.2.4. Исследование способности а-токоферола, менадиоиа и билирубина активировать AhR.
3.3. Исследование цитохромов Р450 подсемейства 1А при совместном введении классического индуктора бснзо (а)пнрена и «слабых» индукторов а-токоферола и менадиоиа и лнганда AhR кверцетпна.
3.3.1. Влияние а-токоферола и менаднона на экспрессию генов CYP1A при совместном введении с бензо (а)пиреном т vivo
3.3.2. Влияние кверцетина на экспрессию генов CYP1A при совместном введении с бензо (а)пиреном in vivo
3.3.3. Влияние менадиоиа и кверцетина на ДНК-связывающую способность AhR
3.4. Ферменты моноокенгеназной системы печени в условиях действия физических факторов
3.4.1. Влияние низкоинтенсивного инфракрасного лазерного излучения на ферменты моноокенгеназной системы печени
3.4.2. Влияние ультразвука низкой интенсивности на ферменты моноокенгеназной системы печени
3.4.3. Влияние электромагнитного излучения сантиметрового диапазона на ферменты моноокенгеназной системы печени 145 3 4 4 Влияние ионизирующего излучения на ферменты моноокенгеназной системы печени
3.4.5. Влияние холодового воздействия на ферменты биотрансформации в печени крыс
3.5. Исследование механизмов индукции активности CYP1A в печени крыс под действием физических факторов
3.5.1. Исследование механизма индукции CYP1A1 под действием ультразвука
3.5.2. Исследование механизма индукции CYPIA1 под действием холода
3.6. Роль эндогенных соединений в индукции CYP1А под действием физических факторов.
3.6.1. Исследование роли билирубина в индукции CYP1А1 в печени под действием ультразвука
3.6.2. Исследование роли а-токофероя и билирубина в индукции CYP1А1 в печени под действием холода
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