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UV-induced Apoptosis (UV-induce + apoptosi)
Selected AbstractsResistance to UV-induced apoptosis in human keratinocytes during accelerated senescence is associated with functional inactivation of p53JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2004V. Chaturvedi Compared to proliferating keratinocytes (KCs), growth-arrested KCs are relatively resistant to UV-light induced apoptosis. When KCs undergo confluency, or following exposure to anti-proliferative agents such as IFN-, plus a phorbol ester,12- O -tetradecanoylyphorbol-13-acetate (TPA), they convert from a proliferative to a nonproliferative state resembling senescence. Since p53 regulates UV-induced apoptosis of KCs, this report further characterizes p53 half-life, post-translational modifications, and transcriptional activity using cultured human KCs and living epidermal equivalents. The half-life of p53 in KCs was longer than fibroblasts (greater than approximately 3 h vs. 30 min). Exposure of proliferating KCs to UV-light induces post-translational modifications of p53 including acetylation of lysine-382 residues. By contrast, KCs undergoing irreversible growth arrest following confluency, or exposure to IFN-, plus TPA, were resistant to UV-induced apoptosis, and failed to undergo the acetylation modification of p53. Exposure of KCs to IFN-, plus TPA reduced total cellular p53 levels and reduced the transcriptional activity of p53. Addition of Trichostatin A (TSA), an inhibitor of de-acetylation, increased acetylation of lysine-382 in confluent KCs, thereby enhancing susceptibility of confluent cultures to UV-induced apoptosis. Pre-treatment of epidermal equivalents with IFN-, plus TPA also blocked UV-light induced increase in p53 levels, and reduced apoptosis. In conclusion, these studies demonstrate that growth arrested KCs may resist UV-light induced apoptosis by inactivating the pro-apoptotic function of p53. J. Cell. Physiol. 198: 100,109, 2004. © 2003 Wiley-Liss, Inc. [source] Modulations of nerve growth factor and Bcl-2 in ultraviolet-irradiated human epidermisJOURNAL OF CUTANEOUS PATHOLOGY, Issue 6 2003Catherine M. Stefanato Background:, Ultraviolet (UV) irradiation to the skin causes apoptosis of keratinocytes. Melanocytes are more resistant to UV-induced apoptosis, due, in part, to high levels of antiapoptotic proteins such as Bcl-2. In vitro studies have shown that nerve growth factor (NGF), a neurotrophic polypeptide, is produced by keratinocytes and exerts a protective role for melanocytes by upregulating Bcl-2. The purpose of this study was to determine NGF and Bcl-2 modulations in UV-irradiated human skin. Methods:, Nine volunteers were irradiated with two minimal erythema doses using solar-simulated UV irradiation. Seventy-two hours post irradiation, skin biopsies were obtained from irradiated and sun-protected skin. The skin specimens were stained with anti-tyrosinase-related protein-1 monoclonal antibody IgG2a (Mel-5), anti-Bcl-2 (monoclonal antibody IgG-kappa), and with anti-NGF (polyclonal antibody IgG). Results:, NGF staining was identified within the cytoplasm of epidermal melanocytes, similar to the staining observed for TRP-1 and Bcl-2. While no significant difference in the number of TRP-1- and Bcl-2-positive melanocytes was observed between irradiated and non-irradiated skin within 72 h, the number of NGF-positive melanocytes decreased significantly, 72 h after UV irradiation (p < 0.024). NGF was also identified within keratinocytes, and while non-irradiated skin exhibited cytoplasmic NGF staining throughout the epidermis, NGF staining was reduced in the lower epidermal layers after UV irradiation. Conclusions:, This is the first in vivo study showing NGF to be present in melanocytes, as well as showing modulations of NGF and Bcl-2 in melanocytes, following solar-simulated UV irradiation. [source] A phosphatidylinositol transfer protein ,-dependent survival factor protects cultured primary neurons against serum deprivation-induced cell deathJOURNAL OF NEUROCHEMISTRY, Issue 3 2006Hanneke Bunte Abstract Selective neuronal loss is a prominent feature in both acute and chronic neurological disorders. Recently, a link between neurodegeneration and a deficiency in the lipid transport protein phosphatidylinositol transfer protein , (PI-TP,) has been demonstrated. In this context it may be of importance that fibroblasts overexpressing PI-TP, are known to produce and secrete bioactive survival factors that protect fibroblasts against UV-induced apoptosis. In the present study it was investigated whether the conditioned medium of cells overexpressing PI-TP, (CM,) has neuroprotective effects on primary neurons in culture. We show that CM, is capable of protecting primary, spinal cord-derived motor neurons from serum deprivation-induced cell death. Since the conditioned medium of wild-type cells was much less effective, we infer that the neuroprotective effect of CM, is linked (in part) to the PI-TP,-dependent production of arachidonic acid metabolites. The neuroprotective activity of CM, is partly inhibited by suramin, a broad-spectrum antagonist of G-protein coupled receptors. Western blot analysis shows that brain cortex and spinal cord express relatively high levels of PI-TP,, suggesting that the survival factor may be produced in neuronal tissue. We propose that the bioactive survival factor is implicated in neuronal survival. If so, PI-TP, could be a promising target to be evaluated in studies on the prevention and treatment of neurological disorders. [source] Molecular mechanisms of UV-induced apoptosisPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 5 2000D. Kulms Sunburn cells, single standing cells with typical morphologic features occurring in UV-exposed skin, have been recognized as keratinocytes undergoing apoptosis following UV irradiation. Induction of apoptosis following UV exposure appears to be a protective mechanism, getting rid off severely damaged cells that bear the risk of malignant transformation. UV-mediated apoptosis is a highly complex process in which different molecular pathways are involved. These include DNA damage, activation of the tumor suppressor gene p53, triggering of cell death receptors either directly by UV or by autocrine release of death ligands, mitochondrial damage and cytochrome C release. Detailed knowledge about the interplay between these pathways will increase our understanding of photocarcinogenesis. This review briefly discusses recent findings concerning the molecular mechanisms underlying UV-induced apoptosis. [source] | |||||||||||||