Genistein inhibits glucocorticoid amplification in adipose tissue by suppression of 11β-hydroxysteroid dehydrogenase type 1

Tagawa, Noriko; Kubota, Sayaka; Kobayashi, Yoshiharu; Kato, Ikuo

doi:10.1016/j.steroids.2014.11.003

Cited by 16 publications

(12 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A more potent H6PD inhibitor could contribute significantly to the study of the biology of H6PD in cancer and metabolic disorders, and for the development of new therapeutics for these diseases. As rucaparib is significantly more potent and selective than the only other known H6PD inhibitor genistein (reported IC 50 > 50 μM) (Tagawa et al, 2015), and structural differences with other PARPi can be harnessed, rucaparib could be a useful starting point for developing more potent and specific H6PD inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Proteome-wide Profiling of Clinical PARP Inhibitors Reveals Compound-Specific Secondary Targets

Knezevic

Wright

Rix

et al. 2016

Cell Chemical Biology

View full text Add to dashboard Cite

Summary PARP inhibitors (PARPi) are a promising class of targeted cancer drugs, but their individual target profiles beyond the PARP family, which could result in differential clinical utility or toxicity, are unknown. Using an unbiased, mass spectrometry-based chemical proteomics approach, we generated a comparative proteome-wide target map of the four clinical PARPi olaparib, veliparib, niraparib, and rucaparib. PARPi as a class displayed high target selectivity. However, in addition to the canonical targets PARP1, PARP2 and several of their binding partners, we also identified hexose-6-phosphate dehydrogenase (H6PD) and deoxycytidine kinase (DCK) as previously unrecognized targets of rucaparib and niraparib, respectively. Subsequent functional validation suggested that inhibition of DCK by niraparib could have detrimental effects when combined with nucleoside analog pro-drugs. H6PD silencing can cause apoptosis and further sensitize cells to PARPi, suggesting that H6PD may be, in addition to its established role in metabolic disorders, a new anticancer target.

show abstract

Section: Discussionmentioning

confidence: 99%

Proteome-wide Profiling of Clinical PARP Inhibitors Reveals Compound-Specific Secondary Targets

Knezevic

Wright

Rix

et al. 2016

Cell Chemical Biology

View full text Add to dashboard Cite

show abstract

“…In the present study, a significant decrease of 11β-HSD1 mRNA expression was observed after exposure to miR-130b-DEX for 48 h when compared with miR-SC-DEX treated cells. As a matter of fact, excess GCs promote lipid deposition and the main regulator of intracellular GCs levels is 11β-HSD1, which converts inactive GCs into bioactive forms [ 50 ]. Inhibition of 11β-HSD1 represents a therapeutic target for treating dexamethasone induced obesity.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-130b attenuates dexamethasone-induced increase of lipid accumulation in porcine preadipocytes by suppressing PPAR-γ expression

et al. 2017

View full text Add to dashboard Cite

In this study, two experiments were conducted to determine the role of miR-130b in dexamethasone (DEX)-induced lipid accumulation. Porcine preadipocytes were treated with 10−6 M DEX for 48 h to investigate effects of DEX in lipid accumulation. Next, in order to illustrate the regulatory role of miR-130b on lipid accumulation induced by DEX, miRNA scrambled control (miR-SC), miR-130b overexpression plasmid and miR-130b inhibitor were respectively transfected into porcine preadipocytes at 24 h before DEX treatment for 48 h (miR-SC-DEX, miR-130b-DEX and miR-130b-inhibitor-DEX). Results showed that 10−6 M DEX significantly increased TG concentration and expression of miR-130b as well as its target gene peroxisome proliferator-activated receptor-γ (PPAR-γ). Dual-luciferase reporter assays indicated that PPAR-γ expression was negatively regulated by miR-130b, while this effect was abolished with cotransfection of miR-130b and miR-130b inhibitor. In addition, miR-130b-DEX did not change cell proliferation but significantly decreased TG concentration and PPAR-γ expression compared to miR-SC-DEX cells, while miR-130b-inhibitor-DEX cells presented opposite results. Furthermore, miR-130b-DEX significantly reduced expression of PPAR-γ downstream factor perilipin 1 as well as adipogenesis genes fatty acid synthase, acetyl coenzyme A carboxylase, 11β hydroxysteroid dehydrogenase type 1 and fat mass and obesity-associated gene, whereas expression as well as enzyme activity of adipose triglyceride lipase and hormone-sensitive lipase were greatly increased. Overall, these results clarified the role of miR-130b in DEX-induced increase of lipid accumulation in porcine preadipocytes, suggesting that miR-130b might be deemed as a novel potential therapeutic target for DEX-induced increase of lipid accumulation, and consequently provide new insights in obesity control.

show abstract

“…In porcine granulosa cells, genistein decreases the activity of cholesterol side-chain cleavage enzyme (P450scc) and 3β-hydroxysteroid dehydrogenase ( 87 ) . Genistein has also been characterised as a non-competitive inhibitor of 11β-hydroxysteroid dehydrogenase type 1, which produces bioactive glucocorticoids, such as cortisol, from inactive precursors ( 88 ) . Disruption of aromatase and 5α-reductase by a number of phyto-oestrogens has also been demonstrated in vitro but this potential activity in mammalian tissues remains controversial ( 2 ) .…”

Section: Mechanisms Of Endocrine Disruption By Isoflavonesmentioning

confidence: 99%

Endocrine disruption by dietary phyto-oestrogens: impact on dimorphic sexual systems and behaviours

Patisaul

2016

Proc. Nutr. Soc.

View full text Add to dashboard Cite

A wide range of health benefits have been ascribed to soya intake including a lowered risk of osteoporosis, heart disease, breast cancer, and menopausal symptoms. Because it is a hormonally active diet, however, soya can also be endocrine disrupting, suggesting that intake has the potential to cause adverse health effects in certain circumstances, particularly when exposure occurs during development. Consequently, the question of whether or not soya phyto-oestrogens are beneficial or harmful to human health is neither straightforward nor universally applicable to all groups. Possible benefits and risks depend on age, health status, and even the presence or absence of specific gut microflora. As global consumption increases, greater awareness and consideration of the endocrine-disrupting properties of soya by nutrition specialists and other health practitioners is needed. Consumption by infants and small children is of particular concern because their hormone-sensitive organs, including the brain and reproductive system, are still undergoing sexual differentiation and maturation. Thus, their susceptibility to the endocrine-disrupting activities of soya phyto-oestrogens may be especially high. As oestrogen receptor partial agonists with molecular and cellular properties similar to anthropogenic endocrine disruptors such as bisphenol A, the soya phyto-oestrogens provide an interesting model for how attitudes about what is ‘synthetic’ v. what is ‘natural,’ shapes understanding and perception of what it means for a compound to be endocrine disrupting and/or potentially harmful. This review describes the endocrine-disrupting properties of soya phyto-oestrogens with a focus on neuroendocrine development and behaviour.

show abstract

Genistein inhibits glucocorticoid amplification in adipose tissue by suppression of 11β-hydroxysteroid dehydrogenase type 1

Cited by 16 publications

References 50 publications

Proteome-wide Profiling of Clinical PARP Inhibitors Reveals Compound-Specific Secondary Targets

Proteome-wide Profiling of Clinical PARP Inhibitors Reveals Compound-Specific Secondary Targets

MicroRNA-130b attenuates dexamethasone-induced increase of lipid accumulation in porcine preadipocytes by suppressing PPAR-γ expression

Endocrine disruption by dietary phyto-oestrogens: impact on dimorphic sexual systems and behaviours

Contact Info

Product

Resources

About