Programmed cell death of stressed keratinocytes and its inhibition by vitamin D: The role of death and survival signaling pathways

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

doi:10.1007/s10495-006-5115-1

Cited by 29 publications

(50 citation statements)

References 47 publications

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“…These studies suggested that 25(OH)D 3 had broad protective effects in many stress model systems. Consistent with our data, the active metabolite of vitamin D 3 , 1,25(OH) 2 D 3 , has been previously reported to protect cells from cell death induction through various pathways including stress [Riachy et al, 2005;Zhang et al, 2005;Diker-Cohen et al, 2006]. In HaCaT keratinocytes, 1,25(OH) 2 D 3 protected the cells from all the examined stress mediated pathways leading to cell death, including TNFa, oxidative stress, hyperosmotic, and heat shock-induced cell death [Diker-Cohen et al, 2006].…”

Section: Discussionsupporting

confidence: 91%

“…In support of our results, 1,25(OH)2D 3 has been shown to decrease the formation of apoptotic cells in epidermis exposed to UV [Hanada et al, 1995] and to reduce cell death in growing hair follicles following treatment with chemotherapeutic drugs [Schilli et al, 1998]. The hormone also protected keratinocytes in vitro from UVB-and TNFa-induced cell death [Diker-Cohen et al, 2006]. As for the protective effect of 25(OH)D 3 in breast epithelial cells, this is the first report to document its anti-stress action.…”

Section: Discussionsupporting

confidence: 86%

“…In line with this, our results demonstrated that 25(OH)D 3 also protected MCF12F breast epithelial cells against H 2 O 2 -induced cell death. However, attenuation of p38 MAPK and JNK activation only partially accounts for the protective effect of 1,25(OH) 2 D 3 in keratinocytes [Diker-Cohen et al, 2006]. Therefore, the mechanism of action of 25(OH)D 3 in the stress response in breast epithelial cells still needs further investigation.…”

Section: Discussionmentioning

confidence: 97%

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Protection against cellular stress by 25‐hydroxyvitamin D₃ in breast epithelial cells

Xiang

Vaishnav

Murillo

et al. 2010

J of Cellular Biochemistry

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25-Hydroxyvitamin D(3) (25(OH)D(3)) is a prohormone and a major vitamin D metabolite. The discovery of (25(OH)D(3)) 1 alpha-hydroxylase in many vitamin D target organs has yielded an increased interest in defining the role(s) of 25(OH)D(3) in these tissues. The etiology of cancer appears to be complex and multi-factorial. Cellular stress (e.g., DNA damage, hypoxia, oncogene activation) has been identified as one of the key factors responsible for initiating the carcinogenesis process. In this study, we investigated whether 25(OH)D(3) protects breast epithelial cells from cellular stress using an established breast epithelial cell line MCF12F. To better elucidate the role of 25(OH)D(3) in the stress response, we used multiple in vitro stress models including serum starvation, hypoxia, oxidative stress, and apoptosis induction. Under all these stress conditions, 25(OH)D(3) (250 nmol/L) treatment significantly protected cells against cell death. Low-serum stress induced p53 expression accompanied with downregulation of PCNA, the presence of 25(OH)D(3) consistently inhibited the alteration of p53 and PCNA, suggesting that these molecules were involved in the stress process and may be potential target genes of 25(OH)D(3). miRNA microarray analysis demonstrated that stress induced by serum starvation caused significant alteration in the expression of multiple miRNAs including miR182, but the presence of 25(OH)D(3) effectively reversed this alteration. These data suggest that there is a significant protective role for 25(OH)D(3) against cellular stress in the breast epithelial cells and these effects may be mediated by altered miRNA expression.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Protection against cellular stress by 25‐hydroxyvitamin D₃ in breast epithelial cells

Xiang

Vaishnav

Murillo

et al. 2010

J of Cellular Biochemistry

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“…4B), indicating that JNK is essential for MMP-9 induction by the cytokine. In accordance with our previous results (Ravid et al, 2002;Diker-Cohen et al, 2006), we confirm here that calcitriol attenuated the activation of JNK by TNFa under conditions relevant to MMP-9 induction (Fig. 4C).…”

Section: The Involvement Of Jnk and P38 Mapk In The Regulation Of Mmpsupporting

confidence: 93%

Upregulation of MMP‐9 production by TNFα in keratinocytes and its attenuation by vitamin D

Bahar‐Shany

Ravid

Koren

2009

Journal Cellular Physiology

Self Cite

122

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MMP-9, a member of the matrix metalloproteinase family that degrades collagen IV and processes chemokines and cytokines, participates in epidermal remodeling in response to stress and injury. Limited activity of MMP-9 is essential while excessive activity is deleterious to the healing process. Tumor necrosis factor (TNFalpha), a key mediator of cutaneous inflammation, is a powerful inducer of MMP-9. Calcitriol, the hormonally active vitamin D metabolite, and its analogs are known to attenuate epidermal inflammation. We aimed to examine the modulation of MMP-9 by calcitriol in TNFalpha-treated keratinocytes. The immortalized HaCaT keratinocytes were treated with TNFalpha in the absence of exogenous growth factors or active ingredients. MMP-9 production was quantified by gelatin zymography and real-time RT-PCR. Activation of signaling cascades was assessed by western blot analysis and DNA-binding activity of transcription factors was determined by EMSA. Exposure to TNFalpha markedly increased the protein and mRNA levels of MMP-9, while pretreatment with calcitriol dose dependently reduced this effect. Employing specific inhibitors we established that the induction of MMP-9 by TNFalpha was dependent on the activity of the epidermal growth factor receptor, c-Jun-N-terminal kinase (JNK), NFkappaB and extracellular signal-regulated kinase-1/2. The effect of calcitriol was associated with inhibition of JNK activation and reduction of DNA-binding activities of the transcription factors activator protein-1 (AP-1) and NFkappaB following treatment with TNFalpha. By down-regulating MMP-9 levels active vitamin D derivatives may attenuate deleterious effects due to excessive TNFalpha-induced proteolytic activity associated with cutaneous inflammation.

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“…Some conditions such as the acute or chronic exposition to UV radiation, dehydration, mechanical lesion, changes in the environment temperature or endogenous insults as inflammation and hypoxia can produce oxidative stress in cells 12 . An aggression example that gathers several conditions implicated in oxidative stress is skin burn, and depending on the extension and the proportion of tissue loss, may lead to unacceptable consequences in a hemodynamical and functional context.…”

Section: Discussionmentioning

confidence: 99%

Keratinocyte growth factor protected cultured human keratinocytes exposed to oxidative stress

et al. 2010

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PURPOSE: To evaluate effects of oxidative stress and supplementation of keratinocyte growth factor (KGF) on cultivated human keratinocytes. METHODS: Oxidative stress was produced through addition of hydrogen peroxide (H2O2) to the culture medium. Cultivated human keratinocytes were divided in 4 groups: Group control (G C), Group KGF (G KGF), Group H2O2 (G H2O2), Group H2O2 and KGF (G H2O2-KGF). Each experiment was accomplished with the same lineage cultivated keratinocytes, in triplicate. Cell viability was evaluated by trypan blue exclusion assay. RESULTS: The results showed that the culture medium supplemented with KGF presented a small rate of cell viability when compared to cells only in culture medium (p<0,001). It demonstrated that only the growth factor does not have protector effects for cells in vitro. However, in front of the oxidative stress produced by addition of hydrogen peroxide to the medium, KGF showed a beneficial effect, protecting cells when compared to the group that suffered hydrogen peroxide action but had not been exposed to KGF (p<0,001). CONCLUSION: KGF determined protection to the primary human keratinocytes exposed to oxidative stress.

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Programmed cell death of stressed keratinocytes and its inhibition by vitamin D: The role of death and survival signaling pathways

Cited by 29 publications

References 47 publications

Protection against cellular stress by 25‐hydroxyvitamin D₃ in breast epithelial cells

Protection against cellular stress by 25‐hydroxyvitamin D₃ in breast epithelial cells

Upregulation of MMP‐9 production by TNFα in keratinocytes and its attenuation by vitamin D

Keratinocyte growth factor protected cultured human keratinocytes exposed to oxidative stress

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Programmed cell death of stressed keratinocytes and its inhibition by vitamin D: The role of death and survival signaling pathways

Cited by 29 publications

References 47 publications

Protection against cellular stress by 25‐hydroxyvitamin D3 in breast epithelial cells

Protection against cellular stress by 25‐hydroxyvitamin D3 in breast epithelial cells

Upregulation of MMP‐9 production by TNFα in keratinocytes and its attenuation by vitamin D

Keratinocyte growth factor protected cultured human keratinocytes exposed to oxidative stress

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Product

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Protection against cellular stress by 25‐hydroxyvitamin D₃ in breast epithelial cells

Protection against cellular stress by 25‐hydroxyvitamin D₃ in breast epithelial cells