Retinoic acid receptor gamma 2 interactions with vitamin D response elements

Koszewski, Nicholas J.; Herberth, Johann; Malluche, Hartmut H.

doi:10.1016/j.jsbmb.2010.04.016

Cited by 13 publications

(7 citation statements)

References 39 publications

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“…PPARγ binds to its heterodimeric partner RXR before binding to DNA [16] . RXR is known to be constitutively expressed in cells and has been shown to heterodimerize with other receptors besides PPARγ, such as the vitamin D receptor [17] .…”

Section: Resultsmentioning

confidence: 99%

Specific Thiazolidinediones Inhibit Ovarian Cancer Cell Line Proliferation and Cause Cell Cycle Arrest in a PPARγ Independent Manner

et al. 2011

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BackgroundPeroxisome Proliferator Activated Receptor gamma (PPARγ) agonists, such as the thiazolinediones (TZDs), have been studied for their potential use as cancer therapeutic agents. We investigated the effect of four TZDs—Rosiglitazone (Rosi), Ciglitazone (CGZ), Troglitazone (TGZ), and Pioglitazone (Pio)—on ovarian cancer cell proliferation, PPARγ expression and PPAR luciferase reporter activity. We explored whether TZDs act in a PPARγ dependent or independent manner by utilizing molecular approaches to inhibit or overexpress PPARγ activity.Principal FindingsTreatment with CGZ or TGZ for 24 hours decreased proliferation in three ovarian cancer cell lines, Ovcar3, CaOv3, and Skov3, whereas Rosi and Pio had no effect. This decrease in Ovcar3 cell proliferation was due to a higher fraction of cells in the G0/G1 stage of the cell cycle. CGZ and TGZ treatment increased apoptosis after 4 hours of treatment but not after 8 or 12 hours. Treatment with TGZ or CGZ increased PPARγ mRNA expression in Ovcar3 cells; however, protein levels were unchanged. Surprisingly, luciferase promoter assays revealed that none of the TZDs increased PPARγ activity. Overexpression of wild type PPARγ increased reporter activity. This was further augmented by TGZ, Rosi, and Pio indicating that these cells have the endogenous capacity to mediate PPARγ transactivation. To determine whether PPARγ mediates the TZD-induced decrease in proliferation, cells were treated with CGZ or TGZ in the absence or presence of a dominant negative (DN) or wild type overexpression PPARγ construct. Neither vector changed the TZD-mediated cell proliferation suggesting this effect of TZDs on ovarian cancer cells may be PPARγ independent.ConclusionsCGZ and TGZ cause a decrease in ovarian cancer cell proliferation that is PPARγ independent. This concept is supported by the finding that a DN or overexpression of the wild type PPARγ did not affect the changes in cell proliferation and cell cycle.

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Section: Resultsmentioning

confidence: 99%

Specific Thiazolidinediones Inhibit Ovarian Cancer Cell Line Proliferation and Cause Cell Cycle Arrest in a PPARγ Independent Manner

et al. 2011

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“… Interactions between vitamin D receptor and retinoid X receptors inducing vitamin D response elements. Adapted from reference 17 . …”

Section: Figmentioning

confidence: 99%

Effects of Vitamin D on Blood Pressure and Endothelial Function

Min

2013

Korean J Physiol Pharmacol

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Vitamin D deficiency is prevalent, primarily due to limited sun exposure, which may be observed in urban areas, or as a result of modern lifestyles. Common myths about vitamin D persist, including that it is mostly obtained from the diet and is only essential for bone and mineral homeostasis. Nonetheless, advances in biomedical science suggest that vitamin D is a hormone that is integral to numerous physiologic functions in most cells and tissues. Therefore, abnormal vitamin D levels may contribute to health disturbances. A number of recent reports on potential associations between vitamin D deficiency and cardiovascular disease have highlighted its role in this system. A focus over the previous decade has been to better understand the mechanisms behind vitamin D regulation and the pathophysiology associated with suboptimal vitamin D levels. Vitamin D deficiency is highly associated with the incidence of cardiovascular diseases, even when considering other well-known risk factors. In this process, the renin-angiotensin system is disrupted, and hypertension and endothelial dysfunction contribute to the risk of cardiovascular disease. Likewise, clinical outcomes upon the normalization of vitamin D levels have been investigated in different patient populations. It makes sense that vitamin D supplementation to improve vitamin D status among vitamin D-deficient individuals could be useful without requiring a sudden lifestyle change. This manuscript provides a brief overview of vitamin D metabolism and the vitamin D receptor. It also summarizes the current clinical research relating to vitamin D supplementation and its effects on hypertension and endothelial dysfunction in cardiovascular medicine.

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“…RXR partners with many nuclear receptors and these effects were originally attributed to its partnering with the vitamin D receptor (VDR), as Vdr tm1Mbd null mice have similar progressive alopecia and anagen inhibition [88, 89]. While it is unlikely that the effects of reduced DGAT1 lead directly to altered vitamin D metabolism or signalling, as they could be reversed by altering dietary vitamin A, an indirect effect of excess vitamin A on vitamin D metabolism or signalling in the hair is possible as interactions between these two vitamins have been seen [90–92]. These Rxra tm4Ipc null mice also have elevated proliferation and defective differentiation in IFE and increased inflammation, which were not seen in Vdr tm1Mbd null mice [93], suggesting other RXR partners are involved.…”

Section: 3 Retinoids In the Hair Folliclementioning

confidence: 99%

Endogenous retinoids in the hair follicle and sebaceous gland

Everts

2012

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Vitamin A and its derivatives (retinoids) are critically important in the development and maintenance of multiple epithelial tissues, including skin, hair, and sebaceous glands, as shown by the detrimental effects of either vitamin A deficiency or toxicity. Thus, precise levels of retinoic acid (RA, active metabolite) are needed. These precise levels of RA are achieved by regulating several steps in the conversion of dietary vitamin A (retinol) to RA and RA catabolism. This review discusses the localization of RA synthesis to specific sites within the hair follicle and sebaceous gland, including their stem cells, during both homeostasis and disease states. It also discusses what is known about the specific roles of RA within the hair follicle and sebaceous gland.

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Retinoic acid receptor gamma 2 interactions with vitamin D response elements

Cited by 13 publications

References 39 publications

Specific Thiazolidinediones Inhibit Ovarian Cancer Cell Line Proliferation and Cause Cell Cycle Arrest in a PPARγ Independent Manner

Specific Thiazolidinediones Inhibit Ovarian Cancer Cell Line Proliferation and Cause Cell Cycle Arrest in a PPARγ Independent Manner

Effects of Vitamin D on Blood Pressure and Endothelial Function

Endogenous retinoids in the hair follicle and sebaceous gland

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