Antiapoptotic action of 1α,25-dihydroxyvitamin D3 in primary human melanocytes

Sauer, Bettina; Ruwisch, Lars; Kleuser, Burkhard

doi:10.1097/00008390-200308000-00002

Cited by 43 publications

(41 citation statements)

References 32 publications

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“…TNF-α has been suggested to damage melanocytes by inducing apoptosis [51]. Vitamin D has been shown to have anti-apoptotic effects on melanocytes and keratinocytes in physiologic concentrations, by acting on the TNF-α, Fas ligand and Bcl-2 pathways [52,53]. …”

Section: Discussionmentioning

confidence: 99%

Analysis of Vitamin D Receptor Gene Polymorphisms in Vitiligo

Aydıngöz

Bingül²,

Doğru‐Abbasoğlu³

et al. 2012

Dermatology

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Background: Vitiligo is a progressive depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. The etiopathogenesis of vitiligo is still unclear. Vitamin D has both stimulatory and protective effects on melanocytes and acts through its nuclear vitamin D receptor (VDR) on target cells. Aim: The aim of this study was to investigate the association between VDR gene polymorphisms and susceptibility to vitiligo. Methods: 98 patients with vitiligo and 216 age- and sex-matched controls recruited from dermatology outpatients attending the same department were included in the study. Genomic DNA was extracted from peripheral blood leukocytes using a DNA isolation kit. The VDR polymorphisms of BsmI, ApaI, TaqI, FokI and Cdx2 were investigated by rapid capillary PCR with melting curve analysis. Differences in genotype distributions and allele frequencies in vitiligo cases versus controls were compared for statistical significance using χ² test. Results: Subjects with TaqI polymorphism had a 2.23-fold increased risk of developing vitiligo. Furthermore, a haplotype analysis showed that BsmI/ApaI/TaqI/FokI/Cdx2 GCCCG wassignificantly overrepresented in the vitiligo patients in comparison with controls (p = 0.031). Conclusion: This study showed that VDR TaqI gene polymorphism and the haplotype BsmI/ApaI/ TaqI/FokI/Cdx2 GCCCG may be considered as novel risk factors in vitiligo.

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Section: Discussionmentioning

confidence: 99%

Analysis of Vitamin D Receptor Gene Polymorphisms in Vitiligo

Aydıngöz

Bingül²,

Doğru‐Abbasoğlu³

et al. 2012

Dermatology

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“…This is interesting because 1,25(OH) 2 D 3 induces apoptosis in many hyperproliferative disorder diseases, such as glioma [30], melanoma and mammary cancer [31]. 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.…”

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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“…It has been shown, however, that melanocytes are stimulated to undergo apoptosis by ways other than the deprivation of growth-promoting agents, such as ultraviolet irradiation (Zhai et al, 1996;Sauer et al, 2003), and treatment with tumor-necrosis factor (Sauer et al, 2003), or Fas (Sharov et al, 2003). It is important to determine if activation of PI 3-kinase or Akt is also effective in the suppression of apoptosis induced by other ways than the deprivation of growth-promoting agents.…”

Section: Figurementioning

confidence: 99%

Phosphatidylinositol 3-Kinase/Akt-Dependent and -Independent Protection Against Apoptosis in Normal Human Melanocytes

Oka

Kageyama

Fukunaga

et al. 2004

Journal of Investigative Dermatology

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Normal human melanocytes require the synergistic action of several growth-promoting agents for their growth in serum-free medium. The ability of four representative growth promoting agents including insulin, 12-O-tetradecanoylphorbol-13-acetate (TPA), basic fibroblast growth factor (bFGF), and 3-isobutyl-1-methylxanthine (IBMX), (iTbI) to protect melanocytes against apoptosis was examined. Also, the involvement of phosphatidylinositol (PI) 3-kinase and Akt, one of the downstream targets of PI 3-kinase, in the survival signaling pathway was examined. The percentage of apoptotic cells was negligible when the cells were grown in the presence of iTbI. Deprivation of iTbI from the culture medium for 72 h caused approximately 30% of melanocytes to undergo apoptosis and this was suppressed to variable extents by the addition of one of the iTbI to the medium. Insulin and TPA protected against apoptosis almost completely, whereas bFGF and IBMX rescued melanocytes from apoptosis to a lesser extent. Wortmannin, an inhibitor of PI 3-kinase, potently inhibited the protective effect of insulin on melanocytes, whereas it did not block the ability of TPA, bFGF, or IBMX to rescue the cells from apoptosis. Furthermore, apoptosis of melanocytes induced by deprivation of iTbI was prevented almost completely by infection with an adenovirus vector encoding a constitutively active mutant of either PI 3-kinase or Akt. These results indicate that melanocytes can operate both PI 3-kinase/Akt-dependent and -independent mechanisms for protection against apoptosis and that activation of the PI 3-kinase/Akt pathway is sufficient for protection against apoptosis induced by deprivation of growth-promoting agents.

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Antiapoptotic action of 1α,25-dihydroxyvitamin D3 in primary human melanocytes

Cited by 43 publications

References 32 publications

Analysis of Vitamin D Receptor Gene Polymorphisms in Vitiligo

Analysis of Vitamin D Receptor Gene Polymorphisms in Vitiligo

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

Phosphatidylinositol 3-Kinase/Akt-Dependent and -Independent Protection Against Apoptosis in Normal Human Melanocytes

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