JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
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2025
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IF 3.5
Liang Yongchao,Huo Hongjin,Wei Wei,Wang Dongxuan,Lu Jingjing,Yi Wenjie,Jiang Fei
Purpose Perfluorooctane sulfonic acid (PFOS) is a representative persistent organic pollutant that has been shown to impair male reproductive function. Epidemiological studies and animal models suggest that vitamin D may modify male reproductive function. However, whether 1α,25(OH) 2 D 3 could mitigate the PFOS-induced damage of Sertoli cells, and the underlying mechanisms remain poorly defined. Methods Mouse Sertoli cell line TM4 were pretreated with or without 10 nM or 100 nM 1α,25(OH) 2 D 3 for 6 h, followed by 100 µM or 200 µM PFOS for 24 h. Cell viability was assessed using the CCK8 assay. Reactive oxygen species (ROS) were detected by fluorescent staining, while malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were measured using commercial kits. siRNA transfection, quantitative real-time PCR (qRT‒PCR), and Western blotting were performed to elucidate the underlying mechanisms. Molecular docking studies were conducted to explore the potential binding of PFOS to Keap1. Results PFOS increased MDA contents, decreased GSH levels, and induced cytotoxicity in mouse Sertoli cells. Mechanistically, PFOS might directly bind to Keap1, facilitating its degradation, leading to persistent activation of the Nrf2-ARE pathway. Conversely, 1α,25(OH) 2 D 3 attenuated PFOS-induced cytotoxicity by alleviating the Nrf2-ARE pathway, a protective effect which was abolished by vitamin D receptor (VDR) knockdown. Conclusion PFOS induces cytotoxicity in Sertoli cells by binding to Keap1 and persistently activating the Nrf2-ARE pathway. 1α,25(OH) 2 D 3 emerges as a promising candidate for mitigating PFOS-induced testicular dysfunction. Graphical abstract
研究领域:
毒理学
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分子生物学
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内分泌学
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生殖生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL BIOCHEMISTRY
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2025
·
IF 2.5
Zi-qing Wang,Li-ping Hao,Zi-xuan Meng,Hao-ran Zhang,Wei-jun Kang,Lian-feng Ai
An LC-MS/MS method was developed and validated for simultaneously quantifying 25-hydroxyvitamin D2, D3, and 1α,25-dihydroxyvitamin D3 in human serum. Protein in 200 μL serum was precipitated with acetonitrile. After centrifugation, the metabolites were derivatized using (diacetoxyiodo)benzene (PIA) and 4-(4-dimethylaminophenyl)-1,2,4-triazolidine-3,5-dione (DMAT) and then quantified by the LC-MS/MS system. The limits of detection (LODs) for the three substances were 10, 10, and 5 pg/mL, and the limits of quantification (LOQs) were 20, 20, and 10 pg/mL. The standard curves for these compounds showed linear regression coefficients (R2)>0.998 over specific concentration ranges. Recoveries were 94.36 %–102.34 % for 25(OH)D2, 92.43 %–103.41 % for 25(OH)D3, and 88.98 %–94.36 % for 1α,25(OH)2D3. The mean serum levels in 109 subjects (consisting of 61 healthy adult males and 59 healthy adult females) were 2.0 ± 1.5 ng/ml (25(OH)D2), 16.4 ± 6.1 ng/ml (25(OH)D3) and 36.6 ± 15.1 pg/ml (1α, 25(OH)2D3).Derivatization of vitamin D metabolites using PIA and DMAT is useful for rapidly determining the serum 25(OH) D2, 25(OH) D3 and 1α,25(OH)2D3 concentrations simultaneously in human serum.
研究领域:
分析化学
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临床医学
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营养学
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产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
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2022
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IF 8.101
Pingcui Xu,Bingfeng Lin,Xuehui Deng,Kai Huang,Yan Zhang,Nani Wang
Ferroptosis plays an essential role in the pathology of osteoporosis . This study investigated whether vitamin D receptor (VDR) activation could protect against age-related osteoporosis through an anti-ferroptosis mechanism. d -galactose (D-gal)-induced mice and VDR-knockout mice were used in the in-vivo study. The VDR activator (1,25(OH) 2 D 3 ) attenuated senescence and ferroptosis in the D-gal-induced bone, as illustrated by downregulated senescence-associated secretory phenotype genes, improved mitochondrial morphology, elevated glutathione , and decreased lipid peroxidation markers (malondialdehyde and 4-hydroxynonenal). The pre-osteoblast MC3T3-E1 cells and primary rat osteoblasts were applied in the in-vitro studies. 1,25(OH) 2 D 3 or ferroptosis inhibitor (ferrostatin-1) treatment downregulated the cellular senescence markers in D-gal-induced osteoblasts. Mechanistically, 1,25(OH) 2 D 3 activated the VDR and its downstream nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway , resulting in the downregulation of lipid peroxidation. Nrf2 knockdown or addition of GPX4 inhibitor (RSL-3) blocked the protective effect of 1,25(OH) 2 D 3 against D-gal-induced ferroptosis and senescence. VDR knockdown impeded the 1,25(OH) 2 D 3 -induced activation of Nrf2/GPX4 pathway in osteoblasts. Proteomics and immunofluorescence analysis confirmed that ferroptosis and suppression of the Nrf2/GPX4 pathway occurred in VDR-knockout mice. Our data demonstrated that ferroptosis played an essential role in age-related osteoporosis. The VDR activation attenuated osteoblast ferroptosis via stimulating the Nrf2/GPX4 signaling pathway.
研究领域:
药理学
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老年学
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骨骼生物学
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细胞信号传导
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DOI
PubMed
高影响因子
Nutrition & Metabolism
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2022
·Vol. 19
·期 1
·1-9
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IF 4.654
Qiu Fubin,Li Rui,Gu Siyu,Zhao Yimin,Yang Linxue
Background Iron and vitamin D (VD) is essential to health. Previous studies have shown that iron homeostasis has a potential effect on VD metabolism, but the mechanism is not fully understood.ObjectivesTo explore the relationship between VD metabolism and iron metabolism, as well as the regulatory mechanism of iron on VD metabolism.Methods 40 male rats were fed adaptively for 7 days and randomly divided into control (C, n = 6 normal diet) group and model (M, n = 24 iron deficient diet) by simple randomization, the latter was used to establish iron deficiency anemia (IDA) model. After 6 weeks of feeding, the M group was randomly divided into: iron deficiency group (DFe), low iron group (LFe), medium iron group (MFe) and high iron group (HFe) by block randomization. Different doses of iron dextran (based on iron content (100 g·bw·d)): 0, 1.1, 3.3 and 9.9 mg) were given respectively. After 4 weeks, the rats were anesthetized with 8% chloral hydrate, Blood (collected from the abdominal aorta), liver and kidney tissues were collected. The serum and tissues were separately packed and frozen at -80℃ for testing.Results The results showed that the levels of hemoglobin (Hb), red blood cell (RBC), serum iron (SI), liver iron, and kidney iron in DFe group were lower than those in the other four groups, while the levels of total iron-binding capacity (TIBC), transferrin (TF) and transferrin receptor (Tfr) in DFe group were higher than those in other groups; The serum levels of 25-(OH)D3 and 1,25-(OH)2D3 in DFe group were significantly lower than those in C group (P < 0.05). The correlation analysis showed that the levels of 25-(OH)D3 and 1,25-(OH)2D3 were negatively correlated with TIBC, TF and Tfr no correlation with SI. Western blotting, immunofluorescence, and q-PCR results showed that compared with C group, the protein and gene expressions of CYP2R1, CYP27A1, and CYP24A1 in DFe group were down-regulated, and the expression of CYP27B1 protein and gene was up-regulated in DFe group.Conclusion Iron may be involved in the metabolism of VD3 by regulating the expression of VD3 hydroxylase, suggesting that appropriate iron supplementation might promote the activation of VD3.
研究领域:
营养学
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生物化学
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药理学
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动物生理学
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DOI
PubMed
高影响因子
POULTRY SCIENCE
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2022
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IF 4.014
Zhengtian Lyu,Haifang Li,Xin Li,Hui Wang,Hongchao Jiao,Xiaojuan Wang,Jingpeng Zhao,Hai Lin
ABSTRACT Fibroblast growth factor 23 ( FGF23 ), a bone-derived hormone, is involved in the reabsorption of phosphate ( P ) and the production of vitamin D hormones in the kidney. However, whether and how FGF23 regulates chicken bone metabolism remains largely unknown. In the present study, we investigated the effect of FGF23 on osteogenic differentiation and mineralization of chicken bone marrow mesenchymal stem cells ( BMSCs ). First, we found that the transcription of FGF23 was inhibited by β-glycerophosphate sodium ( GPS , 5 mM, 10 mM, 20 mM) and 10 −9 M 1, 25-dihydroxyvitamin D3 ( 1, 25(OH) 2 D 3 ), but was stimulated by 10 −7 M 1, 25(OH) 2 D 3 and parathyroid hormone ( PTH , 10 −9 M, 10 −8 M, 10 −7 M). Second, overexpression of FGF23 by the FGF23 adenovirus ( Adv-FGF23 ) suppressed the formation of mineralized nodules ( P < 0.001) and alkaline phosphatase ( ALP ) activity ( P < 0.05) in both differentiated and mineralized osteoblasts. Administration of FGF receptor 3 ( FGFR3 ) inhibitor (50 nM) was sufficient to restore the FGF23-decreased ALP activity ( P < 0.05), but not for the formation of mineralized nodules. In addition, the phosphorylation of ERK increased considerably with Adv-FGF23 overexpression ( P < 0.05). Administration of an ERK-specific inhibitor (10 μM) could down-regulate the phosphorylation of ERK ( P-ERK ) ( P < 0.05) and slightly restored the Adv-FGF23-reduction of ALP activity ( P = 0.08). In summary, our data suggest that GPS, 1, 25(OH) 2 D 3 , and PTH could regulate FGF23 mRNA expression in vitro. FGF23 is a negative regulator of bone remodeling. FGF23 not only inhibits BMSCs osteogenesis through the FGFR3-ERK signaling pathway but also suppresses the mineralization of mature osteoblasts.
研究领域:
骨生物学
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细胞生物学
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分子生物学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
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