Tyrosine kinase inhibitors potentiate the induction of low density lipoprotein receptor gene expression by hepatocyte growth factor

Kanuck, M P; Ellsworth, Jeff L.

doi:10.1016/0024-3205(95)02198-r

Cited by 13 publications

(3 citation statements)

References 37 publications

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“…Confusingly, inhibitors of MEK and tyrosine kinase increased the basal LDLR promoter activity as compared to the vehicle-treated control. MEK pathway has been proved to be essential for LDLR induction by a variety of transcriptional modulators [Singh et al, 1999] and tyrosine kinase has been reported as a potential activator of LDLR expression [Kanuck and Ellsworth, 1995]. Discrepancy of our results with these reports may be explained by the differences of LDLR expression measurements.…”

Section: Ldlr Promoter Region Between à1563contrasting

confidence: 52%

Inhibition of low density lipoprotein receptor expression by long‐term exposure to phorbol ester via p38 mitogen‐activated protein kinase pathway

Choi

Kim

et al. 2005

J of Cellular Biochemistry

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The proximal region -234 to (+58 bp) of low-density lipoprotein receptor (LDLR) is responsible for its up-regulation by sterol regulatory element binding protein (SREBP). However, the mechanism of sterol-independent repression of LDLR has not been determined yet. In this study, we observed that there was an early induction and a later repression of LDLR by phorbol ester (PMA) in SK-Hep1 hepatocarcinoma cells and investigated the mechanisms through which PMA repressed LDLR transcription. SK-Hep1 cells were exposed to PMA and LDLR mRNA was evaluated by RT-PCR and Northern blot analysis. The effect of phorbol ester on LDLR transcriptional activity was studied using transient transfection of LDLR promoter-luciferase constructs. Overexpression of N-SREBP-2, a dominant positive SREBP2, did not reverse the PMA-repressed LDLR promoter activity. Serial deletion of LDLR promoter revealed that the region between -1,563 and -1,326 was responsible for the repression. The pretreatment with SB202190, an inhibitor for p38 mitogen-activated protein kinase pathway (p38-MAPK), but not other signaling inhibitors, reversed the PMA-induced repression. The 24 h-treatment with PMA efficiently arrested the SK-Hep1 cell cycle at G0/G1 as demonstrated by FACS analysis and decreased the 3H-thymidine incorporation. The PMA-induced repression of LDLR transcription may be exerted by the factor(s), not SREBP2, induced or modified by p38-MAPK-mediated signaling pathway and associated with cell cycle blockage.

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Section: Ldlr Promoter Region Between à1563contrasting

confidence: 52%

Inhibition of low density lipoprotein receptor expression by long‐term exposure to phorbol ester via p38 mitogen‐activated protein kinase pathway

Choi

Kim

et al. 2005

J of Cellular Biochemistry

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“…However, ISF decreased average egg weight in 52-weeks old laying hens and egg rate in 44-weeks old laying hens [138]. High ISF concentrations were linked to improved antioxidant effects and immune system as well as a reduction in blood cholesterol levels, improving overall health, and such rich diets decreased the onset of bursa lesions and viral mRNA in chickens infected with infectious bursal disease virus (IBDV) [140,147,150]. Additionally, the ISF GEN affected the reproductive system and bone status of hens and ducks, by capacitating their performance and enhanced strength of their tibia bone [146].…”

Section: Poultrymentioning

confidence: 99%

Isoflavones in Animals: Metabolism and Effects in Livestock and Occurrence in Feed

Grgic

Varga

Novak³

et al. 2021

Toxins

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Soybeans are a common ingredient of animal feed. They contain isoflavones, which are known to act as phytoestrogens in animals. Isoflavones were described to have beneficial effects on farm animals. However, there are also reports of negative outcomes after the consumption of isoflavones. This review summarizes the current knowledge of metabolization of isoflavones (including the influence of the microbiome, phase I and phase II metabolism), as well as the distribution of isoflavones and their metabolites in tissues. Furthermore, published studies on effects of isoflavones in livestock species (pigs, poultry, ruminants, fish) are reviewed. Moreover, published studies on occurrence of isoflavones in feed materials and co-occurrence with zearalenone are presented and are supplemented with our own survey data.

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“…Oestrogens have been shown to lower plasma total cholesterol and LDL-cholesterol (Tikkanen 1996), possibly due to up-regulation of LDL-receptor activity (Abbey et al 1999), and raise HDL-cholesterol, probably due to reduction in hepatic lipase activity and increase the synthesis of apolipoprotein A-I (Muesing et al 1992;Brinton, 1996;Lamon-Fava et al 1999). Similarly, isoflavones (Kanuck & Ellworth, 1995) and/or soyabean protein (Khosla et al 1991;Baum et al 1998) have also been associated with up-regulation of LDL-receptors and increased apolipoprotein A-I synthesis (Lamon-Fava, 2000).…”

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confidence: 99%

Effects of supplementation with purified red clover (Trifolium pratense) isoflavones on plasma lipids and insulin resistance in healthy premenopausal women

et al. 2003

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Consumption of isoflavone-rich soyabean protein is reported to reduce total and LDL-cholesterol, but the specific components responsible are undetermined. In a previous crossover trial we showed that purified isoflavones, derived from red clover (Trifolium pratense ), raised HDL 3 -cholesterol in premenopausal women; however, these findings were inconclusive due to period and carryover effects. In an attempt to overcome this problem, we utilised a parallel study designed to re-examine the effects of purified isoflavones on plasma lipoproteins and markers of insulin resistance in premenopausal women. Twenty-five healthy premenopausal women participated in a double-blind, randomised, parallel study. The treatment group (n 12) consumed a placebo for the first menstrual cycle and an isoflavone supplement (86 mg/d, derived from red clover) for three cycles, while the placebo group (n 13) consumed a placebo supplement for four menstrual cycles. Blood samples were collected weekly during cycles 1, 3 and 4. Supplementation with isoflavones resulted in a 15-fold increase in urinary isoflavone excretion (P, 0·0001). There were no significant effects on total cholesterol, LDL-and HDL-cholesterol, HDL subfractions, triacylglycerol, lipoprotein(a), glucose or insulin concentrations. Our present results indicate that purified isoflavones derived from red clover have no effect on cholesterol homeostasis or insulin resistance in premenopausal women, a group which is at low risk of CHD. Isoflavones: Lipids: Premenopausal womenClinical trials in human subjects have demonstrated the beneficial effects of substituting soyabean protein for animal protein in modifying cardiovascular risk factors (Carroll, 1991;Anderson et al. 1995). However, the specific component(s) responsible for the hypocholesterolaemic properties of soyabean protein are yet to be determined (Potter, 1998). Intervention studies with isoflavone-rich soyabean protein, compared with isoflavone-free soyabean protein, in animals and human subjects have shown reductions in total cholesterol and LDL-cholesterol

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Tyrosine kinase inhibitors potentiate the induction of low density lipoprotein receptor gene expression by hepatocyte growth factor

Cited by 13 publications

References 37 publications

Inhibition of low density lipoprotein receptor expression by long‐term exposure to phorbol ester via p38 mitogen‐activated protein kinase pathway

Inhibition of low density lipoprotein receptor expression by long‐term exposure to phorbol ester via p38 mitogen‐activated protein kinase pathway

Isoflavones in Animals: Metabolism and Effects in Livestock and Occurrence in Feed

Effects of supplementation with purified red clover (Trifolium pratense) isoflavones on plasma lipids and insulin resistance in healthy premenopausal women

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