Главная Случайная страница


Полезное:

Как сделать разговор полезным и приятным Как сделать объемную звезду своими руками Как сделать то, что делать не хочется? Как сделать погремушку Как сделать так чтобы женщины сами знакомились с вами Как сделать идею коммерческой Как сделать хорошую растяжку ног? Как сделать наш разум здоровым? Как сделать, чтобы люди обманывали меньше Вопрос 4. Как сделать так, чтобы вас уважали и ценили? Как сделать лучше себе и другим людям Как сделать свидание интересным?


Категории:

АрхитектураАстрономияБиологияГеографияГеологияИнформатикаИскусствоИсторияКулинарияКультураМаркетингМатематикаМедицинаМенеджментОхрана трудаПравоПроизводствоПсихологияРелигияСоциологияСпортТехникаФизикаФилософияХимияЭкологияЭкономикаЭлектроника






Adrian A. Franke§ and





6. Khosrow Adeli

+ Author Affiliations

1. * Division of Medical Technology, University of Hawaii, Honolulu, HI 96822 2. Department of Laboratory Medicine, Hospital for Sick Children, Toronto, Canada 3. § Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI 96822

1. 2 To whom correspondence should be addressed.

 

Next Section

Abstract

In the present study, the effects of taxifolin, a plant flavonoid, on lipid, apolipoprotein B (apoB), and apolipoprotein A-I (apoA-I) synthesis and secretion were determined in HepG2 cells. Pretreatment of cells with (±)-taxifolin led to an inhibition of cholesterol synthesis in a dose- and time-dependent manner, with an 86 ± 3% inhibition at 200 μM observed within 24 h. As to the mechanism underlying this inhibitory effect, taxifolin was shown to inhibit the activity of HMG-CoA reductase by 47 ± 7%. In addition, cellular cholesterol esterification, and triacylglycerol and phospholipid syntheses, were also significantly suppressed in the presence of taxifolin. ApoA-I and apoB synthesis and secretion were then studied by pulse-chase experiments. ApoA-I secretion was found to increase by 36 ± 10%. In contrast, an average reduction of 61 ± 8% in labeled apoB in the medium was apparent with taxifolin. This effect on secretion appeared not to be exerted at the transcriptional level. Rather, the effect on apoB secretion was found to be exerted in the early stages of apoB degradation and to be sensitive to dithiothreitol (DTT) and insensitive toN-acetylleucyl-leucyl-norleucinal, suggesting a proteolytic pathway involving a DTT-sensitive protease. Fractionation of secreted apoB revealed a slight shift in the distribution of secreted apoB-containing lipoproteins. Cholesteryl ester, rather than triacylglycerol, was shown to be the lipid that primarily regulated apoB secretion. In summary, our data suggest that taxifolin decreases hepatic lipid synthesis with a concomitant decrease and increase in apoB and apoA-I secretion, respectively.—Theriault, A., Q. Wang, S. C. Van Iderstine, B. Chen, A. A. Franke, and K. Adeli. Modulation of hepatic lipoprotein synthesis and secretion by taxifolin, a plant flavonoid.J. Lipid Res.2000. 41: 1969–1979.

Supplementary key words

· apolipoprotein B

· cholesterol

· silymarin

· silybin

· HepG2

Previous SectionNext Section

Introduction

There has been a considerable amount of interest in the benefits of diets rich in flavonoid-containing foods, such as fruits, vegetables, wine, and tea, with respect to cardiovascular disease (CVD) and certain cancers (1). The protective effects of flavonoids against these chronic diseases have been attributed to their free radical-scavenging property. In the case of CVD, flavonoids have been shown to reduce low density lipoprotein (LDL) oxidation, an important step in atherogenesis (2, 3). However, studies have given evidence about the potential role of these flavonoids in reducing blood lipid levels. Investigations by Choi, Yokozawa, and Oura (4) and Jahromi and Ray (5) showed that flavonoid components of Prunus davidiana stem extract and Pterocarpus marsupium heartwood extract reduced cholesterol levels in hyperlipidemic rats. In humans, the intake of soy protein rich in isoflavonoids was shown to significantly reduce serum cholesterol levels (6). In elucidating the molecular mechanism of flavonoid action on cholesterol homeostasis, at least two enzymes involved in cholesterol metabolism were shown to be involved. Work by Wilcox et al. (7) and Borradaile, Carroll, and Kurowska (8) provided evidence that the citrus flavonoids naringenin and hesperetin decreased cholesterol synthesis by inhibiting acyl-CoA:cholesterol acyltransferase (ACAT) activity in HepG2 cells. In contrast, Nassuato et al. (9) demonstrated in rat liver that silybin, the major flavolignan from the fruit of Silybum marianum (syn. Carduus marianus L.), reduced cholesterol synthesis by suppressing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) activity, the rate-limiting enzyme in cholesterol synthesis. Bok et al. (10) showed in vivo that a combination of these two lipogenic enzymes may account for the hypocholesterolemic effect of flavonoids. Despite these findings, it is unclear whether all naturally derived flavonoids (well over 4,000 of them) share these properties. Moreover, whether all flavonoid molecules function to the same degree in cholesterol synthesis remains to be addressed.

View larger version:

· In this page

· In a new window

· Download as PowerPoint Slide

Date: 2015-09-18; view: 226; Нарушение авторских прав; Помощь в написании работы --> СЮДА...



mydocx.ru - 2015-2024 year. (0.005 sec.) Все материалы представленные на сайте исключительно с целью ознакомления читателями и не преследуют коммерческих целей или нарушение авторских прав - Пожаловаться на публикацию