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UV increases skin-derived 1α,25-dihydroxyvitamin D3 production, leading to MMP-1 expression by altering the balance of vitamin D and cholesterol synthesis from 7-dehydrocholesterol
Publication date: Available online 27 August 2019Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): Mi Hee Shin, Yuri Lee, Min-Kyoung Kim, Dong Hun Lee, Jin Ho ChungAbstractThe skin is a unique site in the human body that has the capacity to synthesize the active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), from 7-dehydrocholesterol (7DHC) upon UV irradiation. Keratinocytes express both 25-hydroxylase (CYP27A1 and CYP2R1) and 1α-hydroxylase (CYP27B1), critical enzymes involved in active vitamin D synthesis. Here, we investigated the effect of skin-derived 1α,25(OH)2D3, synthesiz...
Source: The Journal of Steroid Biochemistry and Molecular Biology - August 28, 2019 Category: Biochemistry Source Type: research

1173 Inducible DNA repair of UV photoproducts depends on vitamin D receptor
Ultraviolet radiation (UV) initiates vitamin D synthesis by converting 7-dehydrocholesterol to pre-vitamin D3 that is converted to 25-hydroxyvitamin D3 (25D3) and then 1,25-dihydroxyvitamin D3 (1,25D3). However, UV also generates DNA damage that is repaired by nucleotide excision repair (NER). We tested the hypothesis that vitamin D signaling elicits compensatory responses to the DNA damage incurred during vitamin D synthesis. Treatment of human keratinocytes with either UVB or with 1,25D3 or 25D3 induced the DNA damage recognition protein, XPC, and induction was suppressed by either siRNA targeting the vitamin D receptor ...
Source: Journal of Investigative Dermatology - April 27, 2018 Category: Dermatology Authors: A. Scandurra, C. Wong, T. Kaur Oberoi, D. Oh Tags: Photobiology Source Type: research

Inhibition of pregnane X receptor pathway contributes to the cell growth inhibition and apoptosis of anticancer agents in ovarian cancer cells.
In conclusion, inhibition of PXR-mediated pathways could be a novel means of augmenting sensitivity, or overcoming resistance to anticancer agents for ovarian cancer. PMID: 27572875 [PubMed - in process]
Source: International Journal of Oncology - August 31, 2016 Category: Cancer & Oncology Authors: Masuyama H, Nakamura K, Nobumoto E, Hiramatsu Y Tags: Int J Oncol Source Type: research

Activation of the OVOL1-OVOL2 Axis in the Hair Bulb and in Pilomatricoma.
Abstract OVOL1 and OVOL2, ubiquitously conserved genes encoding C2H2 zinc finger transcription factors in mammals, control epithelial cell proliferation, and differentiation, including those in skin. OVOL1 and OVOL2 expression is coordinately mediated via the Wnt signaling pathway, and OVOL1 negatively regulates OVOL2 expression in a transcriptional manner. Our previous study of OVOL1 expression in human skin revealed that OVOL1 is preferentially expressed in the inner root sheath of the hair follicle. Therefore, we hypothesized that the OVOL1-OVOL2 axis is involved in normal and neoplastic follicular differentiat...
Source: The American Journal of Pathology - February 9, 2016 Category: Pathology Authors: Ito T, Tsuji G, Ohno F, Uchi H, Nakahara T, Hashimoto-Hachiya A, Yoshida Y, Yamamoto O, Oda Y, Furue M Tags: Am J Pathol Source Type: research

Involvement of Pregnane X Receptor in the Impaired Glucose Utilization Induced by Atorvastatin in Hepatocytes.
In conclusion, atorvastatin impaired glucose utilization in hepatocytes via repressing GLUT2 and GCK expressions, which may be partly due to PXR activation. PMID: 26616219 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - November 23, 2015 Category: Drugs & Pharmacology Authors: Ling Z, Shu N, Xu P, Wang F, Zhong Z, Sun B, Li F, Zhang M, Zhao K, Tang X, Wang Z, Zhu L, Liu L, Liu X Tags: Biochem Pharmacol Source Type: research

Ketoconazole induces apoptosis in rat cardiomyocytes through reactive oxygen species-mediated parkin overexpression.
Abstract Azole antifungals such as ketoconazole are generally known to induce a variety of heart function side effects, e.g., long-QT syndrome and ventricular arrhythmias. However, a clear mechanism for the action of ketoconazole in heart cells has not been reported. In the present study, we assessed the correlation between ketoconazole-induced apoptosis and the alteration of genes in response to ketoconazole in rat cardiomyocytes. Cardiomyocyte viability was significantly inhibited by treatment with ketoconazole. Ketoconazole also stimulated H2O2 generation and TUNEL-positive apoptosis in a dose-dependent manner....
Source: Archives of Toxicology - March 19, 2015 Category: Toxicology Authors: Won KJ, Lee KP, Yu S, Lee D, Lee DY, Lee HM, Kim J, Jung SH, Baek S, Kim B Tags: Arch Toxicol Source Type: research

Abstract 4751: 25-hydroxyvitamin D3 induces vitamin D signaling independent of CYP27B1 in non-small cell lung cancer cells
Conclusions NSCLC cells expressing high levels of VDR display increased responsiveness to vitamin D metabolites. Although NSCLC cells express CYP27B1, our results demonstrate that the enzyme may not be required to achieve vitamin D signaling. Rather, 25(OH)D3 may act via the VDR to elicit an anti-tumor responses. The implication of these findings is that dietary supplementation to increase circulating 25(OH)D3 may be beneficial in a subset of NSCLC patients. Funding provided by NIH RO1 CA132844, training grant 5T32CA009072-37 and P30CA47904 Citation Format: Alissa R. Verone, Suzanne Shoemaker, Robert Parise, Jan H. Beumer,...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Verone, A. R., Shoemaker, S., Parise, R., Beumer, J. H., Hershberger, P. A. Tags: Endocrinology Source Type: research