The photoprotective effect of 1,25-dihydroxyvitamin D3 on ultraviolet light B-induced damage in keratinocyte and its mechanism of action

Lee, Joo-heung; Youn, Jai Il

doi:10.1016/s0923-1811(98)00015-2

Cited by 88 publications

(75 citation statements)

References 18 publications

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“…However, such concentrations may well be attained in epidermal cells, the site of autocrine production of 1,25(OH) 2 D 3 (Lehmann et al 2000, Schuessler et al 2001. These results are consistent with previous findings that the hormone protects epidermal cells in vivo and in vitro from UVinduced damage (Lee & Youn 1998, Mason & Holliday 2000 and from apoptosis caused by chemotherapy (Hanada et al 1995, Schilli et al 1998.…”

Section: Discussionsupporting

confidence: 89%

“…Attention has recently been focused on a novel action of active vitamin D metabolites and analogs in the skin, that of the protection of skin and cultured keratinocytes from the damaging effects of UV radiation and chemotherapy (Hanada et al 1995, Lee & Youn 1998, Schilli et al 1998, Mason & Holliday 2000. The aim of the present study was to explore the possibility that the protective action of 1,25(OH) 2 D 3 is associated with modulation of the signaling network that determines cell fate under conditions of stress.…”

Section: Discussionmentioning

confidence: 99%

“…Recent evidence suggests that vitamin D and its active analogs exert a protective effect on keratinocytes under stress. For instance, 1,25(OH) 2 D 3 reduced chemotherapy-induced apoptosis in growing hair follicles (Schilli et al 1998) and protected epidermal keratinocytes from UV-and doxorubicin-induced cell death (Hanada et al 1995, Lee & Youn 1998, Mason & Holliday 2000.…”

Section: Introductionmentioning

confidence: 99%

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Vitamin D inhibits the activation of stress-activated protein kinases by physiological and environmental stresses in keratinocytes

Ravid

Rubinstein²,

Gamady³

et al. 2002

Journal of Endocrinology

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In addition to its known effects on keratinocyte proliferation and differentiation, the hormonal form of vitamin D, 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), has been shown to protect keratinocytes from UV-and chemotherapy-induced damage. Epidermal keratinocytes contain both the machinery needed to produce 1,25(OH) 2 D 3 and vitamin D receptors. The activation of the stress-activated protein kinases (SAPKs), such as c-Jun N-terminal kinase (JNK) and p38, is an early cellular response to stress signals and an important determinant of cell fate. This study examines whether modulation of these SAPKs is associated with the effects of 1,25(OH) 2 D 3 on keratinocytes under stress. HaCaT keratinocytes were exposed to heat shock, hyperosmotic concentrations of sorbitol, the epidermal growth factor receptor tyrosine kinase inhibitor AG1487, the pro-inflammatory cytokine tumor necrosis factor , and H 2 O 2 . These stresses activated both SAPKs. Pretreatment with 1,25(OH) 2 D 3 inhibited the activation of JNK by all stresses and the activation of p38 by heat shock, AG1478 and tumor necrosis factor . Under the same conditions, treatment with 1,25(OH) 2 D 3 protected HaCaT keratinocytes from cytotoxicity induced by exposure to H 2 O 2 and hyperosmotic shock. The effect of 1,25(OH) 2 D 3 was dosedependent, already apparent at nanomolar concentrations, and time-dependent, maximal after a 24-h pre-incubation. We suggest that inhibition of SAPK activation may account for some of the well-documented protective effects of 1,25(OH) 2 D 3 on epidermal cells during exposure to UV or chemotherapy and may also be related to the anti-inflammatory actions of the hormone in skin.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Vitamin D inhibits the activation of stress-activated protein kinases by physiological and environmental stresses in keratinocytes

Ravid

Rubinstein²,

Gamady³

et al. 2002

Journal of Endocrinology

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“…The finding that 1,25(OH) 2 D 3 , even when used at lower doses, is more effective than JN may well be due to its ability to act via 2 pathways, including genomic responses, whereas JN can activate only the nongenomic pathway. For example, induction of the oxygen radical scavenger metallothionein was observed in the skin of UVB-irradiated mice that had been treated topically with 1,25(OH) 2 D 3 (18). Moreover, 1,25(OH) 2 D 3 has been shown to regulate metallothionein gene expression (40) and this may contribute to photoprotection.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous studies, and those of others, provide compelling evidence for novel photoprotective effects of vitamin D compounds in human skin cells and in hairless mice (17)(18)(19)(20)(21)(22)(23)(24). These studies were limited to investigation of the effects of an application of these compounds in acute UVRinduced skin damage, including cell loss and formation of DNA lesions in the form of CPDs and preliminary studies on photo immunosuppression.…”

Section: Introductionmentioning

confidence: 98%

1α,25(OH)2-Vitamin D and a Nongenomic Vitamin D Analogue Inhibit Ultraviolet Radiation–Induced Skin Carcinogenesis

Dixon

Norman

Sequeira

et al. 2011

Cancer Prevention Research

107

153

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Exposure to ultraviolet radiation (UVR) can lead to a range of deleterious responses in the skin. An important form of damage is the DNA photolesion cyclobutane pyrimidine dimer (CPD). CPDs can be highly mutagenic if not repaired prior to cell division and can lead to UV-induced immunosuppression, making them potentially carcinogenic. UVR exposure also produces vitamin D, a prehormone. Different shapes of the steroid hormone 1a,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] can produce biological responses through binding either to its cognate nuclear receptor (VDR) to regulate gene transcription or to the VDR associated with plasma membrane caveolae to produce, via signal transduction, nongenomic physiologic responses. Here, we show that both 1,25(OH) 2 D 3 and 1a,25(OH) 2 -lumisterol (JN), a conformationally restricted analogue that can generate only nongenomic responses, are effective inhibitors of UV damage in an immunocompetent mouse (Skh:hr1) model susceptible to UV-induced tumors. Both 1,25(OH) 2 D 3 and JN significantly reduced UVR-induced CPD, apoptotic sunburn cells, and immunosuppression. Furthermore, these compounds inhibited skin tumor development, both papillomas and squamous cell carcinomas, in these mice. The observed reduction of these UV-induced effects by 1,25 (OH) 2 D 3 and JN suggests a role for these compounds in prevention against skin carcinogenesis. To the best of our knowledge, this is the first comprehensive report of an in vivo long-term biological response generated by chronic dosing with a nongenomic-selective vitamin D steroid.

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The pleiotropic actions of vitamin D

2003

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General knowledge of the role of vitamin D3 in human physiology has been shaped by its discovery as a preventive agent of nutritional rickets, a defect in bone development due to inadequate uptake of dietary calcium. Studies on the function of the hormonal form of vitamin D3, 1alpha,25-dihydroxyvitamin D3, have been greatly accelerated by the molecular cloning and structural analysis of the vitamin D3 receptor, which is a ligand-activated regulator of gene transcription. Molecular genetic techniques including genomics have helped reveal that 1alpha,25-dihydroxyvitamin D3 can control more than calcium homeostasis. It has widespread effects on cellular differentiation and proliferation, and can modulate immune responsiveness, and central nervous system function. Moreover, accumulating epidemiological and molecular evidence suggests that 1alpha,25-dihydroxyvitamin D3 acts as a chemopreventive agent against several malignancies including cancers of the prostate and colon. Here, we survey the most-recent findings and discuss their implications for the potential therapeutic uses of vitamin D analogues.

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The photoprotective effect of 1,25-dihydroxyvitamin D3 on ultraviolet light B-induced damage in keratinocyte and its mechanism of action

Cited by 88 publications

References 18 publications

Vitamin D inhibits the activation of stress-activated protein kinases by physiological and environmental stresses in keratinocytes

Vitamin D inhibits the activation of stress-activated protein kinases by physiological and environmental stresses in keratinocytes

1α,25(OH)2-Vitamin D and a Nongenomic Vitamin D Analogue Inhibit Ultraviolet Radiation–Induced Skin Carcinogenesis

The pleiotropic actions of vitamin D

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