UV-induced extracellular factor from human fibroblasts communicates the UV response to nonirradiated cells

doi:10.1016/0092-8674(84)90421-5

Cell

Volume 37, Issue 3, July 1984, Pages 861-868

https://doi.org/10.1016/0092-8674(84)90421-5 Get rights and content

Abstract

Ultraviolet light enhances the synthesis of at least eight abundant proteins in human fibroblasts within 2 hr. These proteins are identical with those induced by the tumor promoter TPA. The inducing signal is generated by DNA damage, as these proteins are induced by lower doses of UV in fibroblasts from patients with Cockayne's syndrome or Xeroderma pigmentosum. In the supernatant of UV-treated cells, a heat-labile ammonium sulfate precipitable factor of more than 10 kd (EPIF) was detected which, upon transfer to nonirradiated cells, mimicked UV in the UV-induced synthesis of gene products. The response to UV, TPA, or EPIF was inhibited by fluocinolone acetonide, but not by retinoic acid, protease inhibitors, or superoxide dismutase.

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Mitochondrial emitted electromagnetic signals mediate retrograde signaling
2015, Medical Hypotheses
Citation Excerpt :
Electromagnetic irradiation with wavelength 810 nm could be used as a replacement for growth factor in human progenitor cells in vitro [110]. UV light induces the synthesis of a group of proteins in human fibroblasts which are identical to those produced by the tumor-promoter TPA (12-O-Tetradecanoylphorbol-13-acetate) [111]. In summary, evidence from different scientific fields clearly shows that the exogenous and endogenous electromagnetic fields with various frequencies are active biological factors as they can regulate several cellular activities, including nuclear transcriptional activity.
Recent evidence shows that mitochondria regulate nuclear transcriptional activity both in normal and cell stress conditions, known as retrograde signaling. Under normal mitochondrial function, retrograde signaling is associated with mitochondrial biogenesis, normal cell phenotype and metabolic profile. In contrast, mitochondrial dysfunction leads to abnormal (oncogenic) cell phenotype and altered bio-energetic profile (nucleus reprogramming). Despite intense research efforts, a concrete mechanism through which mitochondria determine the group of genes expressed by the nucleus is still missing.
The present paper proposes a novel hypothesis regarding retrograde signaling. More specifically, it reveals the mitochondrial membrane potential (MMP) and the accompanied strong electromagnetic field (EF) as key regulatory factors of nuclear activity. Mitochondrial emitted EFs extend in long distance and affect the function of nuclear membrane receptors. Depending on their frequencies, EFs can directly activate or deactivate different groups of nuclear receptors and so determine nuclear gene expression. One of the key features of the above hypothesis is that nuclear membrane receptors, besides their own endogenous or chemical ligands (hormones, lipids, etc.), can also be activated by electromagnetic signals.
Moreover, normal MMP values (about −140 mV) are associated with the production of high ATP quantities and small levels of reactive oxygen species (ROS) while the hyperpolarization observed in all cancer cell types leads to a dramatic fall in ATP production and an analogous increase in ROS. The diminished ATP and increased ROS production negatively affect the function of all cellular systems including nucleus. Restoration of mitochondrial function, which is characterized by the fluctuation of MMP and EF values within a certain (normal) range, is proposed as a necessary condition for normal nuclear function and cancer therapy.
Antioxidant enzymes and the mechanism of the bystander effect induced by ultraviolet C irradiation of A375 human melanoma cells
2013, Mutation Research - Genetic Toxicology and Environmental Mutagenesis
Citation Excerpt :
Irradiated cells transmit signals to neighboring non-irradiated cells to trigger varied responses [23–29]. This phenomenon is known as the bystander effect (BE) [29–34]. Signals for the BE are transmitted both through gap junctions and released factors from the irradiated cells [29].
Irradiated cells generate dynamic responses in non-irradiated cells; this signaling phenomenon is known as the bystander effect (BE). Factors secreted by the irradiated cells communicate some of these signals. Conditioned medium from UVC-irradiated A375 human melanoma cells was used to study the BE. Exposure of cells to conditioned medium induce cell-cycle arrest at the G2/M transition. Although conditioned medium treatment, by itself, did not alter cell viability, treated cells were more resistant to the lethal action of UVC or H₂O₂. This protective effect of conditioned medium was lost within 8 h. Apoptotic or autophagic cell death was not involved in this resistance. Exposure to conditioned medium did not influence the rate of DNA repair, as measured by NAD⁺ depletion. The activities of catalase and superoxide dismutase were elevated in cells exposed to conditioned medium, but returned to normal levels by 8 h post-treatment. These results indicate a close correlation between BE-stimulated antioxidant activity and cellular sensitivity. Cell-cycle arrest and stimulation of antioxidant activity may account for the resistance to killing that was observed in bystander cells exposed to UVC or H₂O₂ treatment and are consistent with the role of the BE as a natural defense function triggered by UVC irradiation.
Radiation Induced Cytoplasmic Signaling
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This chapter discusses the cellular responses brought about by the damaging effects of radiation. Radiation induces active processes in cells. Apoptosis and the activation of inflammatory cells require cellular signaling and even new protein synthesis. Radiation affects a plethora of cellular constituents. Radiation results in damage and inactivation of target molecules. To cope with protein damage, cells possess recognition systems for damaged or non-physiological molecules that trigger signaling events, exemplified by the unfolded protein response and the system of pattern recognition receptors. The best example of radiation induced damage recognition and signaling has been elaborated for DNA lesions. DNA damage triggers the formation of protein complexes that mediate the activation of protein kinase cascades. UV causes purine and pyrimidine crosslinks that may also occur in mRNA molecules and form blocks for ribosomes. Most effects of UV radiation on cytoplasmic signaling are mediated by the radiation induced reactive oxygen intermediates (ROIs). The ROIs create a pro-oxidant state that affects redox sensitive molecules. Proteins consume most of the ROIs generated inside the cells, resulting in protein modification. These modifications are reversible and thereby potentially suitable for signal transduction. There are numerous cysteine and methionine containing signal transducing proteins whose oxidation or reduction has been implicated in cellular signaling. PTPs are important components of signal regulation. Their inactivation by irradiation is highly relevant for cellular signaling.
A copper-responsive transcription factor, CRF1, mediates copper and cadmium resistance in Yarrowia lipolytica
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Citation Excerpt :
Most of the damaging effects of irradiation are due to the production of free radicals in the cell, and such effects are increased in the presence of heavy metals. It has also been described that after exposure to UV light certain cells produce several metallothionein-inducing factors (42, 43). Accordingly, we compared the ability of Δcrf1 and wild-type strains to survive UV irradiation.
The dimorphic yeast Yarrowia lipolytica is more resistant to high copper concentrations thanSaccharomyces cerevisiae. This differential tolerance to copper ions has been observed in several strains arising from non-related isolates. To investigate the molecular basis of this resistance, we obtained several copper-sensitive mutants. By complementation of one of them, we isolated the YlCRF1 gene encoding for a copper-binding transcription factor of 411 amino acids homologous to ScAce1p, CgAmt1p, and ScMac1p. Naturally occurring copper-sensitive strains lack the CRF1 allele. TheYlCRF1 transcript is not induced by the addition of copper to the medium. Gene disruption demonstrated thatYlCRF1 is responsible for a 4- to 5-fold increase in Y. lipolytica copper tolerance. We further show that strain Δcrf1 is more sensitive to cadmium but not to other metals. The role of YlCrf1p as a copper-sensitive transcription factor is supported by the finding that the protein is immunolocalized in the nucleus during growth in copper-supplemented but not in copper-free medium. However, in contrast to the S. cerevisiae strain mutated in the metallothionein transcription activator ACE1, Y. lipolytica strain Δcrf1 is still able to increase metallothionein (MTP) mRNA levels in response to copper addition.CRF1 deletion does not affect superoxide dismutase (SOD) activity either. Our data suggest the existence of one or more different target genes for Crf1p, other than MTP orSOD1, and support its role as a novel copper-responsive transcription factor involved in metal detoxification.
Effects of ionizing radiation in targeted and nontargeted cells
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Radiation-induced signal transduction. Mechanisms and consequences
1999, Comptes Rendus de l'Academie des Sciences - Serie III
Over a dose range up to 50 Gy of low-LET (linear energy transfer) ionizing radiation and up to 5 k)/m2 UVB, mammalian cells convert molecular damage into productive response (mostly gain of function). By inactivation of negative regulatory components, such as protein tyrosine phosphatases as one mechanism discovered, the balance between restraining and stimulating influences is disturbed and an increase in signal flow results. Also DNA damage causing transcriptional arrest produces a signalling cascade of as yet unknown details. Such stimulation of the intracellular communication network can lead to apoptosis, elevated cell cycling and differentiation processes possibly including repair and recombination. The outcome likely depends on integration of all signals received which is as yet ill-understood. Although accurate determinations of low-dose inductions have not been achieved for technical reasons, the dose-response curves of induced signal transduction likely show threshold characteristics, in contrast to the direct consequences of DNA damage.

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Cell

ArticleUV-induced extracellular factor from human fibroblasts communicates the UV response to nonirradiated cells

Abstract

J. Biol. Chem.

Cell

Cell

Cell

Cell

Cell

Adv. Cancer Res.

Cellular oncogenes and retroviruses

Ann. Rev. Biochem.

A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels

Eur. J. Biochem.

Abnormal oxygen metabolism in Bloom Syndrome?

Prog. Mutation Res.

A polypeptide secreted by transformed cells that modulates human plasminogen activator production

Science

Growth factors from murine sarcoma virus-transformed cells

Clastogenic activity from Bloom syndrome fibroblast cultures

Tumor promoter phorbol 12-myristate 13-acetate induces a clastogenic factor in human lymphocytes

Growth factors in mammalian cell culture

Ann. Rev. Biochem.

Article
UV-induced extracellular factor from human fibroblasts communicates the UV response to nonirradiated cells