Entosis is induced by ultraviolet radiation.
Ontology highlight
ABSTRACT:
SUBMITTER: Chen R
PROVIDER: S-EPMC8353511 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:UV irradiation and other stress-activated signals activate the Jun N-terminal kinase (JNK, SAPK) pathway. The induction of JNK activity results in the activation of proto-oncogene c-Jun and activator protein-1 (AP-1) transcriptional activity. Data presented here show that UV mediated the activation of JNK correlated with UV-induced apoptosis and that overexpression of a dominant negative JNK blocked UV-induced apoptosis. However, the molecular events that lead to JNK activation in response to UV treatment are not clear. In this report, we provide evidence that a Fas receptor binding protein, Daxx, mediates UV-induced JNK activation and apoptosis. A dominant negative Daxx, coding for the C-terminal region (112 amino acids) of Daxx, was constructed and used in the experiments. Our data show that overexpression of the dominant negative Daxx partially inhibits UV-induced JNK phosphorylation in 293 cells. Inhibition of JNK phosphorylation resulted in the inhibition of c-Jun activation upon UV irradiation. Our data also show that the inhibition of JNK activation by dominant negative Daxx correlates with the reduced rate of apoptotic death of 293 cells after UV irradiation. Surprisingly, overexpression of wild-type Daxx also inhibited UV-induced apoptosis, suggesting that Daxx competes for Fas receptor binding sites with other proapoptotic factors such as FADD. In addition, overexpression of a dominant negative mutant of FADD did not affect UV-induced JNK activation but does inhibit UV-induced apoptosis. These results suggest that UV-induced JNK activation is not sufficient but required for induction of apoptosis.
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Project description:Human papillomaviruses are causally associated with 5% of human cancers. The recent discovery of a papillomavirus (MmuPV1) that infects laboratory mice provides unique opportunities to study the life cycle and pathogenesis of papillomaviruses in the context of a genetically manipulatable host organism. To date, MmuPV1-induced disease has been found largely to be restricted to severely immunodeficient strains of mice. In this study, we report that ultraviolet radiation (UVR), specifically UVB spectra, causes wild-type strains of mice to become highly susceptible to MmuPV1-induced disease. MmuPV1-infected mice treated with UVB develop warts that progress to squamous cell carcinoma. Our studies further indicate that UVB induces systemic immunosuppression in mice that correlates with susceptibility to MmuPV1-associated disease. These findings provide new insight into how MmuPV1 can be used to study the life cycle of papillomaviruses and their role in carcinogenesis, the role of host immunity in controlling papillomavirus-associated pathogenesis, and a basis for understanding in part the role of UVR in promoting HPV infection in humans.
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Project description:The purpose of the present study was to evaluate the role of Hrd1 in the ultraviolet (UV) radiation induced photoaging and explore its potential mechanism. The nude mice were exposed to the UVA/UVB irradiation for 10 weeks. The animals were subcutaneously injected with AAV5-NC, Hrd1-shRNA-AAV5, or Hrd1-overexpression-AAV5. The HSF cells were also transfected with Ad-NC, Ad-shRNA-Hrd1, or Ad-Hrd1, and irradiated by UVA/UVB stimulation. The clinical skin samples were harvested for detecting Hrd1 and IGF-1R expressions. As a result, the knockdown of Hrd1 attenuated the histopathological alteration and collagen degradation in UV-induced nude mice. The inhibition of Hrd1 by Hrd1-shRNA-AAV5 and Ad-shRNA-Hrd1 inhibited the Hrd1 expression and promoted IGF-1R, Type I collagen and type III collagen in mice and HSF cells. The overexpression of Hrd1 exerted the reverse effect. The Co-IP assay also indicated the interaction between Hrd1 and IGF-1R. Hrd1-mediated IGF-1R downregulation and collagen degradation were also observed in clinical skin samples. In conclusion, the present results demonstrated that Hrd1 degraded IGF-1R and collagen formation in UV-induced photoaging.
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Project description:A complete carcinogen, ultraviolet B (UVB) radiation (290-320 nm), is the major cause of skin cancer. UVB-induced systemic immunosuppression that contributes to photocarcinogenesis is due to the glycerophosphocholine-derived lipid mediator platelet-activating factor (PAF). A major question in photobiology is how UVB radiation, which only absorbs appreciably in the epidermal layers of skin, can generate systemic effects. UVB exposure and PAF receptor (PAFR) activation in keratinocytes induce the release of large numbers of microvesicle particles (MVPs; extracellular vesicles ranging from 100 to 1000 nm in size). MVPs released from skin keratinocytes in vitro in response to UVB (UVB-MVPs) are dependent on the keratinocyte PAFR. Here, we used both pharmacologic and genetic approaches in cells and mice to show that both the PAFR and enzyme acid sphingomyelinase (aSMase) were necessary for UVB-MVP generation. Our discovery that the calcium-sensing receptor is a keratinocyte-selective MVP marker allowed us to determine that UVB-MVPs leaving the keratinocyte can be found systemically in mice and humans following UVB exposure. Moreover, we found that UVB-MVPs contained bioactive contents including PAFR agonists that allowed them to serve as effectors for UVB downstream effects, in particular UVB-mediated systemic immunosuppression.
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Project description:Releasing promoter-proximally-paused RNA polymerase II (RNAPII) by the positive transcription elongation factor b (P-TEFb) is a central regulatory step of eukaryotic mRNA synthesis. The nuclear activity of P-TEFb is controlled mainly by the 7SK small nuclear RNP (snRNP) which sequesters active P-TEFb into inactive 7SK/P-TEFb snRNP. Here we demonstrate that under normal culture conditions, the lack of 7SK snRNP has only a minor impact on global RNAPII transcription and promoter-proximal pausing without detectable consequences on cell growth and proliferation. However, upon ultraviolet (UV) light-induced DNA damage, cells lacking 7SK have a defective transcriptional response and highly reduced viability. Both UV-induced release of ‘lesion-scanning’ polymerases and activation of key early responsive genes are compromised in the absence of 7SK. We show that proper induction of 7SK-dependent UV-responsive genes, namely efficient release of paused RNAPII and recruitment of key elongation factors, requires P-TEFb activity directly mobilized from the nucleoplasmic 7SK/P-TEFb snRNP.
2021-03-30 | GSE147055 | GEO
Project description:This paper aims to highlight the pharmacological aspects of listed herbal skincare products used for the treatment of various disorders caused due to ultraviolet radiation. The pharmacological aspects include safety and efficacy validation as per regulatory guidelines following internationally accepted scientific principles for their development of skincare products. Herbal products have always been used traditionally for the treatment of various skin ailments and have become more prevalent because of their safety and high efficacy benefits. The incorporation of synthetic molecules and chemical substances in the different medicinal and pharmaceutical formulations is the leading cause of the dermal toxicity. Therefore, the developments of herbal skincare products containing scientifically validated herbal ingredients have better acceptance, respect, and belief in the society. The listed herbal products in this review can help take forward the commercial development of skincare products for therapeutic as well as beauty care purposes from such plants.
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Project description:If the genome contains outlier sequences extraordinarily sensitive to environmental agents, these would be sentinels for monitoring personal carcinogen exposure and might drive direct changes in cell physiology rather than acting through rare mutations. New methods, adductSeq and freqSeq, provided statistical resolution to quantify rare lesions at single-base resolution across the genome. Primary human melanocytes, but not fibroblasts, carried spontaneous apurinic sites and TG sequence lesions more frequently than UV-induced cyclobutane pyrimidine dimers (CPDs). UV exposure revealed hyperhotspots acquiring CPDs up to 170 fold more frequently than the genomic average; these sites were more prevalent in melanocytes. Hyperhotspots were disproportionately located near genes, particularly for RNA-binding proteins, with the most-recurrent hyperhotspots at a fixed position within two motifs: one occurring at ETS1 transcription factor binding sites, known to be UV targets, and at sites of mTOR/TOP-tract translation regulation; the second occurring at A2-15TTCTY, which developed "dark CPDs" after UV exposure, repaired CPDs slowly, and had accumulated CPDs prior to the experiment. Motif locations active as hyperhotspots differed between cell types. Melanocyte CPD hyperhotspots aligned precisely with recurrent UV signature mutations in individual gene promoters of melanomas and with known cancer drivers. At sunburn levels of UV exposure, every cell would have a hyperhotspot CPD in each of the ~20 targeted cell pathways, making hyperhotspots act as epigenetic marks. Purpose: These experiments searched for genomic sites in human primary fibroblasts and melanocytes that are extraordinarily sensitive to DNA damage, primarily cyclobutane pyrimidine dimers (CPDs) induced by UVC or UVB radiation. They separately detected abasic sites and other spontaneous DNA damage when present.
2020-04-14 | GSE137226 | GEO
Project description:BackgroundPlant absorption of ultraviolet (UV) radiation can result in multiple deleterious effects to plant tissues. As a result, plants have evolved an array of strategies to protect themselves from UV radiation, particularly in the UV-B range (280-320 nm). A common plant response to UV exposure is investment in phenolic compounds that absorb damaging wavelengths of light. However, the inverse phenomenon - plant reflectance of UV to protect plant tissues - has not previously been explored. In a paired experiment, we expose half of our sample (N = 108) of insect-pollinated plants of the cultivar Zinnia Profusion Series to UV radiation, and protect the other half from all light < 400 nm for 42 days, and measure leaf and flower reflectance using spectroscopy. We compare UV-B reflectance in leaves and flowers at the beginning of the experiment or flowering, and after treatment.ResultsWe find that plants protected from UV exposure downregulate UV-B reflectance, and that plants exposed to increased levels of UV show trends of increased UV-B reflectance.ConclusionsOur results indicate that upregulation of UV-B reflecting pigments or structures may be a strategy to protect leaves against highly energetic UV-B radiation.
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