UV irradiation induces downregulation of bcl-2 expression in vitro and in vivo

Isoherranen, Kirsi; Sauroja, Ilari; Jansén, Christer T.; Punnonen, Kari

doi:10.1007/s004030050396

Cited by 35 publications

(31 citation statements)

References 25 publications

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“…It has also been demonstrated that the level of the antiapoptotic protein Bcl-2 is downregulated following UV exposure and that this contributes to UV-induced apoptosis (Isoherranen et al, 1999;Washio et al, 1999;Dunkern et al, 2001). The Bcl-2 gene promoter has been shown to bind E2F1 and to be transcriptionally activated by E2F1 overexpression (Gomez-Manzano et al, 2001).…”

Section: E2f1 Status Does Not Affect Activation Of Mitogenactivated Pmentioning

confidence: 99%

Regulation of epidermal apoptosis and DNA repair by E2F1 in response to ultraviolet B radiation

et al. 2005

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The E2F1 transcription factor regulates the expression of genes involved in cell proliferation, apoptosis and DNA repair. Following DNA damage, E2F1 is phosphorylated and stabilized, but the physiological role of E2F1 in the response to DNA damage is unclear. We find that mice lacking E2F1 have increased levels of epidermal apoptosis compared to wild-type mice following exposure to ultraviolet B (UVB) radiation. Moreover, transgenic overexpression of E2F1 in basal layer keratinocytes suppresses apoptosis induced by UVB. Inhibition of UVB-induced apoptosis by E2F1 is unexpected given that most studies have demonstrated a proapoptotic function for E2F1. E2F1-mediated suppression of apoptosis does not involve alterations in mitogen-activated protein kinase activation or Bcl-2 downregulation in response to UVB and is independent of p53. Instead, inhibition of UVBinduced apoptosis by E2F1 correlates with a stimulation of DNA repair. Mice lacking E2F1 are impaired for the removal of DNA photoproducts, while E2F1 transgenic mice repair UVB-induced DNA damage at an accelerated rate compared to wild-type mice. These findings suggest that E2F1 participates in the response to UVB by promoting DNA repair and suppressing apoptosis.

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Section: E2f1 Status Does Not Affect Activation Of Mitogenactivated Pmentioning

confidence: 99%

Regulation of epidermal apoptosis and DNA repair by E2F1 in response to ultraviolet B radiation

et al. 2005

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“…The anti-apoptotic bcl-2 protein is known to decrease after UVB irradiation, and its decrease has been correlated the induction of UVB-induced apoptosis (40). A431 cells were therefore UVB irradiated with low and intermediate doses and at 1, 2, and 3 h after irradiation cell lysates were tested for bcl-2 expression.…”

Section: Bcl-2 Persists During the Delay Of The Executioner Phase Of mentioning

confidence: 99%

Ultraviolet B Radiation-Induced Cell Death: Critical Role of Ultraviolet Dose in Inflammation and Lupus Autoantigen Redistribution

Caricchio

McPhie

Cohen

2003

The Journal of Immunology

147

116

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The nuclear self-Ags targeted in systemic lupus erythematosus translocate to the cell membrane of UV-irradiated apoptotic keratinocytes and may represent an important source of self-immunization. It is hard to understand how the noninflammatory milieu accompanying most apoptosis might provoke an immunogenic response leading to autoantibodies. We have found that the precise amount of keratinocyte UV exposure is crucial in determining the rate of apoptosis, the amount of inflammatory cytokine production, and the degree of autoantigen translocation. Low doses of UVB (≤15 mJ/cm2) promptly induced a normal, caspase-dependent apoptosis, while intermediate doses of UV-B (35 mJ/cm2) caused apoptosis with altered morphology, slower DNA fragmentation, and poly(ADP-ribose) polymerase degradation accompanied by increased Bcl-2. High doses of UVB (80 mJ/cm2) induced instead necrosis. We observed IL-1 production upon intermediate and high UVB doses. Nuclear Ag redistribution was also markedly UV dose dependent: at low doses, Sm, Ku, and DNA translocated to the surfaces of early apoptotic cells. At intermediate doses, these Ags concentrated on the cell membrane when the nucleus was still visible. At high doses, these autoantigens diffused into the cytoplasm and were released into the supernatant. Taken together, the results show that low-dose UVB induces prompt noninflammatory apoptosis. In contrast, intermediate and high doses of UVB induce proinflammatory apoptosis and necrosis, where the production of inflammatory cytokines is accompanied by exposure and release of autoantigens. The key importance of the UV dose on the fate of apoptotic keratinocytes and on their potential immunogenicity should help clarify the role of UVB in inducing systemic lupus erythematosus autoimmunity.

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“…In many systems, UV irradiation triggers p53 phosphorylation which in turn activates proapoptotic genes and induces apoptosis through mitochondria [6]. In addition, it has been shown that UV irradiation induces apoptosis by downregulating Bcl-2 [39]. We examined the ability of UV to induce apoptosis in GK and HeLa cells.…”

Section: Discussionmentioning

confidence: 99%

Iridovirus Bcl-2 protein inhibits apoptosis in the early stage of viral infection

et al. 2007

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The grouper iridovirus (GIV) belongs to the family Iridoviridae, whose genome contains an antiapoptotic B-cell lymphoma (Bcl)-2-like gene. This study was carried-out to understand whether GIV blocks apoptosis in its host. UV-irradiated grouper kidney (GK) cells underwent apoptosis. However, a DNA fragmentation assay of UV-exposed GK cells after GIV infection revealed an inhibition of apoptosis. The UV- or heat-inactivated GIV failed to inhibit apoptosis, implying that a gene or protein of the viral particle might contribute to an apoptosis inhibitory function. The DNA ladder assay for GIV-infected GK cells after UV irradiation confirmed that apoptosis inhibition was an early process which occurred as early as 5 min post-infection. A GIV-Bcl sequence comparison showed distant sequence similarities to that of human and four viruses; however, all possessed the putative Bcl-2 homology (BH) domains of BH1, BH2, BH3, and BH4, as well as a transmembrane domain. Northern blot hybridization showed that GIV-Bcl transcription began at 2 h post-infection, and the mRNA level significantly increased in the presence of cycloheximide or aphidicolin, indicating that this GIV-Bcl is an immediate-early gene. This was consistent with the Western blot results, which also revealed that the virion carries the Bcl protein. We observed the localization of GIV-Bcl on the mitochondrial membrane and other defined intracellular areas. By immunostaining, it was proven that GIV-Bcl-expressing cells effectively inhibited apoptosis. Taken together, these results demonstrate that GIV inhibits the promotion of apoptosis by GK cells, which is mediated by the immediate early expressed viral Bcl gene.

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UV irradiation induces downregulation of bcl-2 expression in vitro and in vivo

Cited by 35 publications

References 25 publications

Regulation of epidermal apoptosis and DNA repair by E2F1 in response to ultraviolet B radiation

Regulation of epidermal apoptosis and DNA repair by E2F1 in response to ultraviolet B radiation

Ultraviolet B Radiation-Induced Cell Death: Critical Role of Ultraviolet Dose in Inflammation and Lupus Autoantigen Redistribution

Iridovirus Bcl-2 protein inhibits apoptosis in the early stage of viral infection

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