Vitamin D Protects Keratinocytes from Apoptosis Induced by Osmotic Shock, Oxidative Stress, and Tumor Necrosis Factor

Diker-Cohen, Talia; Koren, Ruth; Liberman, Uri; Ravid, Amiram

doi:10.1196/annals.1299.064

Cited by 39 publications

(35 citation statements)

References 6 publications

(4 reference statements)

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“…Anti-apoptotic actions of 1,25-(OH) 2 D 3 have been described in keratinocytes (45,46), osteoblasts (47), lymphocytes (48), thyrocytes (49), and osteosarcoma cells (50). The functions are consistent with the positive physiological role of 1,25-(OH) 2 D 3 in regulating the survival and differentiation of cells of skin, bone, and the immune system.…”

Section: Discussionsupporting

confidence: 52%

Suppression of Death Receptor-mediated Apoptosis by 1,25-Dihydroxyvitamin D3 Revealed by Microarray Analysis

Zhang

Bao

et al. 2005

Journal of Biological Chemistry

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Vitamin D 3 (VD)2 is a steroid hormone best known for its role in calcium homeostasis. Its deficiency causes rickets in children and osteomalacia in adults. VD also regulates the proliferation and differentiation of normal and malignant cells of many tissue types. Because sunlight controls the first step of VD synthesis, namely, the photoconversion of 7-dehydrocholesterol to vitamin D 3 (1), the hormone is considered a "sun" medicine that is effective for the treatment and/or prevention of type II rickets, osteoporosis, autoimmune disorders, as well as epithelial cancers of many types.Ovarian cancer (OCa) is a fatal disease with an overall 5-year survival rate of about 40%. OCa mortality and incidence rates are lower in countries within 20 degrees of the equator (2) where there is a high amount of sunlight. In the United States, women between the ages of 45 and 54 living in the North have 5 times the OCa mortality rate of women living in Southern states (3). The inverse correlation between sunlight exposure and OCa mortality indicates that decreased synthesis of VD may contribute to OCa initiation and/or progression. This idea has been further substantiated by recent studies (4 -7) showing that 1,25-dihydroxyvitamin D 3 (1,25-(OH) 2 D 3 ), the active form of VD, inhibits the growth of multiple OCa cell lines (4 -6) and OVCAR3 tumor xenografts in nude mice (7).Effects of VD are mediated through the vitamin D receptor (8), which is a member of the steroid/thyroid receptor superfamily of ligand-regulated transcription factors. In response to the activation by 1,25-(OH) 2 D 3 , the receptor recruits multiple co-activators, including members of the p160 SRC family (9), which are associated with histone acetyltransferase activity, and the DRIP complex (10), which serves as a mediator between the vitamin D receptor and RNA polymerase II complex. Recent studies (11) have suggested that the anti-tumor activity of VD is mediated through its effect on gene transcription. In OCa cells, we have shown that the transcriptional up-regulation of GADD45 is essential for the 1,25-(OH) 2 D 3 -induced cell cycle arrest at the G 2 /M checkpoint (4). 1,25-(OH) 2 D 3 also increases p27 protein stability in OCa cells through down-regulation of Skp2 and cyclin E mRNA to induce cell cycle arrest at the G 1 /S checkpoint (6). These studies suggest that the action of 1,25-(OH) 2 D 3 through the nuclear activation of vitamin D receptor is important for the anti-tumor activity of the hormone in OCa.Because the anti-tumor activity of 1,25-(OH) 2 D 3 is mediated through regulation of gene expression, a more complete understanding of the mechanism underlying 1,25-(OH) 2 D 3 action in OCa cells necessitates identification of changes in gene expression induced by the hormone. In the present study, we profile transcriptional changes in OVCAR3 cells induced by 1,25-(OH) 2 D 3 using multiple independent microarray analyses. We concentrated our subsequent analysis to a few apoptosis-related genes from this list. Our studies reveal that 1,25-(OH) 2 D 3...

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Section: Discussionsupporting

confidence: 52%

Suppression of Death Receptor-mediated Apoptosis by 1,25-Dihydroxyvitamin D3 Revealed by Microarray Analysis

Zhang

Bao

et al. 2005

Journal of Biological Chemistry

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“…In contrast, it elicits no proapoptotic effects in normal astrocytes, melanocytes and mammary cells [39]. More importantly, 1,25(OH) 2 D 3 protects keratinocytes from apoptosis initiated by UV radiation or chemotherapy [40]. Calbindin has a major role in protecting against apoptosis in different cell types [41].…”

Section: Discussionmentioning

confidence: 99%

Effects of 22-Oxa-Calcitriol on Podocyte Injury in Adriamycin-Induced Nephrosis

et al. 2011

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Background: In various animal studies, vitamin D has been shown to have a significant effect on reduction of proteinuria and the progression of kidney disease. However, little is known on its renoprotective effect in adriamycin (ADR)-induced nephrosis mice. The present study was intended to determine the therapeutic benefit of 22-oxa-calcitriol (OCT), a vitamin D analog, in reducing proteinuria and its renoprotective effect, i.e. preventing podocyte injury on ADR-induced nephrosis mice. Methods: Three experimental groups were used as follows: (1) nephrosis mice, established by a single intravenous injection of ADR; (2) ADR+OCT mice, nephrosis mice treated with OCT, and (3) mice treated only with OCT as the control group. Podocyte injury was assessed by podocyte apoptosis using the TUNEL assay, podocyte counting, podocyte-specific expressed protein by immunofluorescence and Western blot analysis, and foot process effacement using electron microscopy. Results: Lower proteinuria was observed in ADR+OCT mice. Improvement in glomerulosclerosis and interstitial fibrosis, and prevention of glomerular hyperfiltration were observed in ADR+OCT mice. Immunofluorescence and Western blot analyses showed restoration of downregulated expression of nephrin, CD2AP and podocin. Nevertheless, dendrin expression was not restored. An insignificant reduction in podocyte numbers was found in ADR+OCT mice. Complete foot process effacement was partially prevented in ADR+OCT mice. Conclusions: The results indicate that OCT reduces podocyte injury and has renoprotective effects in ADR nephrosis mice.

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“…In contrast, 1,25(OH) 2 D 3 inhibits apoptosis in normal astrocytes, melanocytes [32], and mammary cells. 1,25(OH) 2 D 3 protects keratinocytes from the apoptosis initiated by UV radiation or chemotherapy [33], and primary melanocytes from that initiated by TNF-α and UV irradiation, the latter through induction of sphingosine 1-phosphate. Although the beneficial effects of 1,25(OH) 2 D 3 on proteinuria and renal morphology in SNX rats have been described in earlier studies [10], our study is the first to demonstrate the preventive effect of 1,25(OH) 2 D 3 on podocyte apoptosis in PAN nephropathy rats, which has potentially important clinical consequences.…”

Section: Discussionmentioning

confidence: 99%

1,25-Dihydroxyvitamin D<sub>3</sub> Prevents Puromycin Aminonucleoside-Induced Apoptosis of Glomerular Podocytes by Activating the Phosphatidylinositol 3-Kinase/Akt-Signaling Pathway

et al. 2009

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Background: Accumulating evidence suggests that vitamin D and its analogs reduce proteinuria and slow the decline in kidney function in chronic kidney disease. Given a rich literature identifying podocyte apoptosis as an early step in the pathophysiological progression to proteinuria and glomerulosclerosis, we hypothesized that vitamin D protects podocytes from undergoing apoptosis. Methods: A rat model of podocyte apoptosis was created by a single intravenous injection of 100 mg·kg^–1 puromycin aminonucleoside (PAN) and received either solvent or 1,25(OH)₂D₃ treatment. Proteinuria, podocyte apoptosis, the expression of nephrin protein and mRNA, TGF-β/Smad and phosphatidylinositol 3-kinase (PI3K)/Akt-signaling pathway were evaluated, respectively. Results: PAN induced massive proteinuria, serum creatinine elevation and podocyte apoptosis in PAN nephropathy rats, which was associated with the loss of nephrin, an adhesion molecule specific for the glomerular slit and the reduced of p-Akt/Akt ratio. Moreover, PAN induced foot process retraction, redistribution of nephrin and the activation of TGF-β/Smad-signaling pathway. Compared with PAN nephropathy rats, 1,25(OH)₂D₃ significantly prevented loss of nephrin, foot process retraction and podocyte apoptosis by stimulating Akt phosphorylation and suppressing TGF-β/Smad-signaling pathway. Conclusion: 1,25(OH)₂D₃ reduced the PAN-induced podocyte apoptosis and loss of nephrin in PAN nephropathy rat. The anti-apoptotic effects of 1,25(OH)₂D₃on podocytes may be partly attributable to activation of a PI3K/Akt survival pathway.

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Vitamin D Protects Keratinocytes from Apoptosis Induced by Osmotic Shock, Oxidative Stress, and Tumor Necrosis Factor

Cited by 39 publications

References 6 publications

Suppression of Death Receptor-mediated Apoptosis by 1,25-Dihydroxyvitamin D3 Revealed by Microarray Analysis

Suppression of Death Receptor-mediated Apoptosis by 1,25-Dihydroxyvitamin D3 Revealed by Microarray Analysis

Effects of 22-Oxa-Calcitriol on Podocyte Injury in Adriamycin-Induced Nephrosis

1,25-Dihydroxyvitamin D<sub>3</sub> Prevents Puromycin Aminonucleoside-Induced Apoptosis of Glomerular Podocytes by Activating the Phosphatidylinositol 3-Kinase/Akt-Signaling Pathway

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