Membranal effects of phytoestrogens and carboxy derivatives of phytoestrogens on human vascular and bone cells: New insights based on studies with carboxy-biochanin A

Sömjen, Dalia; Kohen, Förtüne; Lieberherr, Michèle; Gayer, Batya; Schejter, Eduardo; Katzburg, Sara; Limor, Rona; Sharon, Orli; Knoll, Esther; Posner, Gary H.; Kaye, Alvin M.; Stern, Naftali

doi:10.1016/j.jsbmb.2004.12.029

Cited by 30 publications

(52 citation statements)

References 39 publications

(62 reference statements)

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“…43 Although the effects of all phytoestrogens tested here on 25-hydroxyvitamin D 3 -1␣-hydroxylase activity are stimulatory, the phytoestrogens exert diverse effects on cell growth; eg, BA and cBA increase DNA synthesis in VSMCs, and similar concentrations of genistein actually inhibit DNA synthesis in VSMCs. [21][22][23]42 The increase in 25-hydroxyvitamin D 3 -1␣-hydroxylase activity induced by E 2 , cBA, and BA also requires the steroid molecule to enter the cell because it cannot be reproduced by the macroprotein conjugates of E 2 or the phytoestrogens that are incapable of traversing the cell membrane. Hence, these effects on 25-hydroxyvitamin D 3 -1␣-hydroxylase appear to be mediated through classic genomic effects.…”

Section: Discussionmentioning

confidence: 99%

“…21,22 The observed increments in 1,25(OH) 2 D 3 concentration were 40Ϯ23% (PϽ0.05), 55ϩ13% (PϽ0.05), and 47Ϯ13% (PϽ0.05) for E 2 , BA, and genistein, respectively (Figure 3). Additionally, the noncalcemic synthetic analog of 1,25(OH) 2 D 3 JKF also increased 1,25(OH) 2 D 3 production by 83Ϯ13% (PϽ0.01) (Figure 3).…”

Section: Effect Of Pth and Estrogenic Compounds On The Enzymatic Convmentioning

confidence: 96%

“…21 E 2 -6-CMO was conjugated to ovalbumin (Ov) via a 2-step reaction as described previously. 21,22 In the first step, E 2 -6-CMO was conjugating in dry dioxane with N-hydroxysuccinimide and carbodiimide. In the second step, the N-hydroxysuccinimide ester derivative of E 2 -6-CMO in dioxane was bound to Ov.…”

Section: Preparation Of Estradiol Macromolecular Conjugatesmentioning

confidence: 99%

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25-Hydroxyvitamin D ₃ -1α-Hydroxylase Is Expressed in Human Vascular Smooth Muscle Cells and Is Upregulated by Parathyroid Hormone and Estrogenic Compounds

et al. 2005

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Section: Discussionmentioning

confidence: 99%

Section: Effect Of Pth and Estrogenic Compounds On The Enzymatic Convmentioning

confidence: 96%

Section: Preparation Of Estradiol Macromolecular Conjugatesmentioning

confidence: 99%

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25-Hydroxyvitamin D ₃ -1α-Hydroxylase Is Expressed in Human Vascular Smooth Muscle Cells and Is Upregulated by Parathyroid Hormone and Estrogenic Compounds

et al. 2005

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“…Binding was terminated by four successive washes with ice-cold binding medium. Enhancement solution (300µl/well) was then added to the cells, and the samples (200µl) were collected for fluorescence determination using an Arcus time resolved fluorometer (Wallac, Turku, Finland) [21,23,24]. Specific binding was defined as total binding of Europium protein conjugates minus binding in the presence of a 500 folds excess of conjugated estrogenic compounds or E 2 where appropriate.…”

Section: Competitive Binding Assay For Membrane Estrogen Binding Actimentioning

confidence: 99%

“…The compounds we analyzed were the licorice derived compounds glabrene (Gla) and glabridin (Glb) [19], the carboxy-derivative of daidzein (cD) [20] and the phytoestrogen from soy the daidzein (D) [21] similar to the synthetic derivatives of D the DT56a (femarelle) [22]. …”

Section: Introductionmentioning

confidence: 99%

Phytoestrogenic Compounds and Their Synthetic Analogs, Contrary to Estradiol- 17b Stimulates Human Derived Female Cultured Bone Cells in Hyperglycemic Conditions

Sömjen¹,

Katzburg²,

Tamir³

et al. 2011

J Steroids Hormon Sci

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Cultured female-derived human osteoblasts (hObs) responded by different parameters to the phytoestrogens: daidzein (D), glabrene (Gla) and glabridin (Glb), to their synthetic derivatives; carboxy-daidzein (cD) and to estradiol-17β (E 2 ). Since the skeletal protective effects of estrogens are not discernible in diabetic women, we tested the effects of these compounds on hObs grown in growth medium with high glucose (HG; 9.0g/L; 44mM) compared to normal glucose (NG; 4.5g/L; 22mM) using the stimulation of creatine kinase specific activity (CK) and 3 [H] thymidine incorporation into DNA (DNA) as hormonal responsiveness markers. HG slightly increased DNA and CK in hObs.Stimulations by E 2 was abolished and by cD and D was slightly decreased in HG, but not by Gla and Glb in both age groups. Growing hObs in HG upregulated the expression of mRNA of both ER and ERβ in cells from pre-but not from post-menopausal women. Cells from both age groups express also mRNA for 25 hydroxy vitamin D 3 1-α hydroxylase and showed enzymic activity which were down-regulated by HG in both age groups. Whether Gla and Glb act differentially via ERs and/or 1-α hydroxylase is not yet established.Since these compounds are active even in HG, they might be used for treating hyperglycemic/diabetic women. Journal of Steroids & Hormonal Science Materials and Methods ReagentsAll reagents used were analytical grade. Estradiol-17β (E 2 ), daidzein (D) and the creatine kinase (CK) assay kit were purchased from Sigma Chemicals Co. (St. Louis, MO). Carboxy-D (cD) was synthesized by us [20], licorice products: Gla and Glb were produced by us [19]. Cell culturesHuman bones were obtained from biopsies of patients undergoing corrective surgery following accidental injury, hip or knee replacement. All patients (women and men) were healthy, non-osteoporotic and not receiving hormonal replacement treatment. Three groups were defined: Pre-menopausal women, ranging between 37-55 years old, (n=5). Post-menopausal women, ranging between 60-84 years old, (n=5). The non-enzymic method for isolation and culture of human bone cells and their characterization as osteoblasts was described previously [12]. Briefly, samples of the trabecular surface of the iliac crest or long bones were cut into 1mm 3 pieces and extensively and repeatedly washed with phosphate buffered saline (PBS) to remove blood components. The explants, with no enzymatic digestion, were seeded in 100mm diameter tissue culture dishes and incubated in DMEM medium without Ca ++ (to avoid fibroblastic growth [12], containing 10% fetal calf serum (FCS) and antibiotics. Cell outgrowth from the bone explants was apparent after 6-10 days. First passage cells were seeded at a density of 3x10 5 cells per 35mm tissue culture dish in phenol red free DMEM with 10% charcoal stripped FCS and incubated at 37°C in 5% CO 2 . To obtain "high glucose" (HG) conditions, the medium including the FCS, was supplemented with glucose up to a final concentration of 44nM (9.0gm/ liter). Glucose concentration in the regula...

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Diabetes modulates differentially creatine kinase‐specific activity responsiveness to estradiol‐17β and to raloxifene in rat organs

Sömjen

Shen

Stern

et al. 2006

J of Cellular Biochemistry

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Diabetes mellitus increases the risk for CVD in women. While there is considerable evidence suggesting beneficial effects of estrogen on decreasing lipid peroxidation, atherosclerotic processes, and cardiovascular diseases, diabetes negates most estrogen protective effects as well as the skeletal protective effects of estrogens, which are not discernable in diabetic women. In the present study, we examined the in vivo effects of estradiol-17beta (E2), on creatine kinase (CK)-specific activity, in estrogen-responsive organs from healthy and diabetic rats. Healthy or diabetic (streptozotocin-induced) female rats were injected with either E2 (10-50 microg/rat) or raloxifene (Ral; 500-1,000 microg/rat). Twenty-four hours following the injection, animals were sacrificed; their organs removed and assayed for CK-specific activity. CK-specific activity in different organs [Left ventricle of heart (Lv), uterus (Ut), aorta (Ao), para uterine adipose tissue (Ad), epiphyseal cartilage (Ep), and diaphyseal bone (Di)] from healthy animals, was stimulated with increased doses of E2, with maximum at 20 microg/rat. Age-matched diabetic female rats exhibited a remarkable decreased response to E2 in all organs except Ut. In contrast, the response to Ral was not altered in diabetic rats. Similar results were observed in organs from ovariectomized female rats (Ovx), healthy or diabetic. These results support our previous in vitro findings, demonstrating that hyperglycemia decreases CK response to E2 but not to Ral in cultured human vascular and bone cells. In summary, diabetes mellitus decreases CK response to E2 but not that of Ral in skeletal and vascular tissues. The decreased response to E2 detected in organs derived from diabetic rats might be due to changes in nuclear and/or membrane estrogen receptors and/or other genomic and non-genomic pathways, as was shown in in vitro cellular models.

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Membranal effects of phytoestrogens and carboxy derivatives of phytoestrogens on human vascular and bone cells: New insights based on studies with carboxy-biochanin A

Cited by 30 publications

References 39 publications

25-Hydroxyvitamin D ₃ -1α-Hydroxylase Is Expressed in Human Vascular Smooth Muscle Cells and Is Upregulated by Parathyroid Hormone and Estrogenic Compounds

25-Hydroxyvitamin D ₃ -1α-Hydroxylase Is Expressed in Human Vascular Smooth Muscle Cells and Is Upregulated by Parathyroid Hormone and Estrogenic Compounds

Phytoestrogenic Compounds and Their Synthetic Analogs, Contrary to Estradiol- 17b Stimulates Human Derived Female Cultured Bone Cells in Hyperglycemic Conditions

Diabetes modulates differentially creatine kinase‐specific activity responsiveness to estradiol‐17β and to raloxifene in rat organs

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Membranal effects of phytoestrogens and carboxy derivatives of phytoestrogens on human vascular and bone cells: New insights based on studies with carboxy-biochanin A

Cited by 30 publications

References 39 publications

25-Hydroxyvitamin D 3 -1α-Hydroxylase Is Expressed in Human Vascular Smooth Muscle Cells and Is Upregulated by Parathyroid Hormone and Estrogenic Compounds

25-Hydroxyvitamin D 3 -1α-Hydroxylase Is Expressed in Human Vascular Smooth Muscle Cells and Is Upregulated by Parathyroid Hormone and Estrogenic Compounds

Phytoestrogenic Compounds and Their Synthetic Analogs, Contrary to Estradiol- 17b Stimulates Human Derived Female Cultured Bone Cells in Hyperglycemic Conditions

Diabetes modulates differentially creatine kinase‐specific activity responsiveness to estradiol‐17β and to raloxifene in rat organs

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25-Hydroxyvitamin D ₃ -1α-Hydroxylase Is Expressed in Human Vascular Smooth Muscle Cells and Is Upregulated by Parathyroid Hormone and Estrogenic Compounds

25-Hydroxyvitamin D ₃ -1α-Hydroxylase Is Expressed in Human Vascular Smooth Muscle Cells and Is Upregulated by Parathyroid Hormone and Estrogenic Compounds