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FoxO1 AND Vitamin D

Peter Petschner, Noemi Balogh, Csaba Adori, Viola Tamasi, Sahel Kumar, Gabriella Juhasz, Gyorgy Bagdy
The active ingredient of ecstasy, ±3,4-methylenedioxymethamphetamine (MDMA), in addition to its initial reinforcing effects, induces selective and non-selective brain damage. Evidences suggest that the hippocampus (HC), a central region for cognition, may be especially vulnerable to impairments on the long-run, nevertheless, transcription factors that may precede and regulate such chronic changes remained uninvestigated in this region. In the current study, we used gene-set enrichment analysis (GSEA) to reveal possible transcription factor candidates responsible for enhanced vulnerability of HC after MDMA administration...
2018: Frontiers in Pharmacology
Yuma Hirose, Takumi Onishi, Shinji Miura, Yukino Hatazawa, Yasutomi Kamei
Vitamin D is known to be effective for the prevention of muscle atrophy, such as age-related sarcopenia. However, vitamin D action in skeletal muscle tissue and muscle cells is largely unknown. We previously found that a transcription factor, FOXO1 gene expression, was induced in various muscle atrophy conditions causing muscle atrophy by upregulating atrophy-related genes, including atrogin 1 (ubiquitin ligase) and cathepsin L (lysosomal proteinase). In this study, we found that vitamin D inhibited FOXO1-mediated transcriptional activity in a reporter gene assay...
2018: Journal of Nutritional Science and Vitaminology
Ludmilla Bär, Martina Feger, Abul Fajol, Lars-Oliver Klotz, Shufei Zeng, Florian Lang, Berthold Hocher, Michael Föller
Fibroblast growth factor 23 (FGF23) is produced by bone cells and regulates renal phosphate and vitamin D metabolism, as well as causing left ventricular hypertrophy. FGF23 deficiency results in rapid aging, whereas high plasma FGF23 levels are found in several disorders, including kidney or cardiovascular diseases. Regulators of FGF23 production include parathyroid hormone (PTH), calcitriol, dietary phosphate, and inflammation. We report that insulin and insulin-like growth factor 1 (IGF1) are negative regulators of FGF23 production...
May 29, 2018: Proceedings of the National Academy of Sciences of the United States of America
Yi Xiong, Yixin Zhang, Na Xin, Ying Yuan, Qin Zhang, Ping Gong, Yingying Wu
1α,25-Dihydroxyvitamin D3 (1,25(OH)2 D3 ) is the active form of vitamin D, which is responsible for reducing the risk for diabetes mellitus (DM), decreasing insulin resistance, and improving insulin secretion. Previous studies have shown that 1,25(OH)2 D3 inhibited the activity of FoxO1, which has been implicated in the regulation of glucose metabolism. However, its function and mechanism of action in DM-induced energy disorders and also in bone development remains unclear. Here, using in vitro and in vivo approaches including osteoblast-specific, conditional FoxO1-knock-out mice, we demonstrate that 1,25(OH)2 D3 ameliorates abnormal osteoblast proliferation in DM-induced oxidative stress conditions and rescues the impaired glucose and bone metabolism through FoxO1 nuclear exclusion resulting from the activation of PI3K/Akt signaling...
December 8, 2017: Journal of Biological Chemistry
Yi Xiong, Yixin Zhang, Na Xin, Ying Yuan, Qin Zhang, Ping Gong, Yingying Wu
Diabetes mellitus (DM) remarkably affects bone metabolism and causes multiple skeletal disorders, which are associated with the increased oxidative stress that activates Forkhead family of transcription factors (FoxOs). 1α,25-Dihydroxy vitamin D3 (1,25(OH)2 D3 ), the hormonally active form of vitamin D, plays a potential role in the prevention of glucose tolerance. However, its mechanism of action in high glucose-induced energy disorders remains unclear. In vitro study shows that 1,25(OH)2 D3 promotes osteogenesis in high glucose-induced oxidative stress mainly results from increased osteoblasts proliferation and decreased apoptosis...
November 2017: Journal of Steroid Biochemistry and Molecular Biology
Tara C Brennan-Speranza, David Mor, Rebecca S Mason, John R Bartlett, Gustavo Duque, Itamar Levinger, Pazit Levinger
Muscle function is often impaired in patients with knee osteoarthritis (OA), with reduced strength and increased pain. The role of vitamin D and the vitamin D-endocrine pathway in muscle health has recently been placed in the spotlight, with various groups reporting positive effects on muscle development, function and health. Recently, it has been shown that uptake into muscle of the specialized vitamin D binding protein (DBP) is dependent on the endocytic receptor, megalin. Here we analyse circulating vitamin D, and muscle DBP, megalin and the cognate vitamin D receptor (VDR) in patients with knee OA and compare them to asymptomatic controls...
October 2017: Journal of Steroid Biochemistry and Molecular Biology
Songcang Chen, S Armando Villalta, Devendra K Agrawal
Prospective epidemiological studies have consistently shown a relationship between vitamin D deficiency, insulin resistance, and type 2 diabetes mellitus (DM2). This is supported by recent trials showing that vitamin D supplementation in prediabetic or insulin-resistant patients with inadequate vitamin D levels improves insulin sensitivity. However, the molecular mechanisms underlying vitamin D deficiency-induced insulin resistance and DM2 remain unknown. Skeletal muscle insulin resistance is a primary defect in the majority of patients with DM2...
March 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Anne Jørgensen, Martin Blomberg Jensen, John Erik Nielsen, Anders Juul, Ewa Rajpert-De Meyts
The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has anti-proliferative, pro-apoptotic, and pro-differentiating effects in somatic cancer cells in vitro and in vivo. 1,25(OH)2D3 also augments the anti-tumor effects of several chemotherapeutic agents, including cisplatin, which may have clinical relevance. Given the pro-differentiation effect of vitamin D recently demonstrated in testicular germ cell tumors (TGCTs), we hypothesized that 1,25(OH)2D3 could be a beneficial adjunctive to existing chemotherapy regime used to treat these tumors...
July 2013: Journal of Steroid Biochemistry and Molecular Biology
Guy Eelen, Lieve Verlinden, Mark B Meyer, Rik Gijsbers, J Wesley Pike, Roger Bouillon, Annemieke Verstuyf
Forkhead Box O (FoxO) transcription factors and Sestrins (SESN) are highly conserved and related stress-responsive proteins that protect the organism against age-related pathologies. For FoxOs, growing evidence shows a crucial role in osteoblast function. Here we investigated the role of different FoxO and SESN isoforms in 1,25(OH)2D3-treated MC3T3-E1 osteoblasts. 1,25(OH)2D3 rapidly and strongly induced the expression of SESN1 and FoxO3a but down-regulated the expression of SESN3 and FoxO1. SESN2 and FoxO4 levels were hardly affected by 1,25(OH)2D3...
July 2013: Journal of Steroid Biochemistry and Molecular Biology
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