Bcl-2, Bax, and c-Fos expression correlates to RPE cell apoptosis induced by UV-light and daunorubicin

Liang, Ye; Jørgensen, A.; Kaestel, C G; Wiencke, Anne Katrine; Lui, Ge Ming; Cour, Morten la; Røpke, Carsten; Nissen, Mogens Holst

doi:10.1076/0271-3683(200001)2011-hft025

Cited by 30 publications

(19 citation statements)

References 30 publications

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“…In fact, expression of pro-and antiapoptotic Bcl-2 family proteins is altered by oxidative stress, and these proteins represent a major factor, insofar as the outcome of the apoptotic signaling, because cell survival reflects the predominance of one set of proteins over the other. In the RPE and retina, oxidative stress, increased by several factors including light exposure or reactive oxygen species, shifts the balance of Bcl-2 family protein expression toward those that favor cell damage (44,45). Because our results show oxidative-stress-induced changes in the expression of Bcl-2 proteins, they imply that the early RPE response to oxidative stress includes transcriptional, translational, and͞or posttranslational events upstream of the mitochondrial apoptotic step.…”

Section: Discussionmentioning

confidence: 57%

Neuroprotectin D1: A docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress

Mukherjee

Marcheselli

Serhan

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

693

690

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Docosahexaenoic acid (DHA) is a lipid peroxidation target in oxidative injury to retinal pigment epithelium (RPE) and retina. Photoreceptor and synaptic membranes share the highest content of DHA of all cell membranes. This fatty acid is required for RPE functional integrity; however, it is not known whether specific mediators generated from DHA contribute to its biological significance. We used human ARPE-19 cells and demonstrated the synthesis of 10,17S-docosatriene [neuroprotectin D1 (NPD1)]. This synthesis was enhanced by the calcium ionophore A-23187, by IL-1␤, or by supplying DHA. Under these conditions, there is a time-dependent release of endogenous free DHA followed by NPD1 formation, suggesting that phospholipase A2 releases the mediator's precursor. Added NPD1 potently counteracted H2O2͞tumor necrosis factor ␣ oxidative-stress-triggered apoptotic RPE DNA damage. NPD1 also up-regulated the antiapoptotic proteins Bcl-2 and Bcl-xL and decreased proapoptotic Bax and Bad expression. Moreover, NPD1 (50 nM) inhibited oxidative-stress-induced caspase-3 activation. NPD1 also inhibited IL-1␤-stimulated expression of cyclooxygenase 2 promoter transfected into ARPE-19 cells. Overall, NPD1 protected RPE cells from oxidative-stress-induced apoptosis, and we predict that it will similarly protect neurons. This lipid mediator therefore may indirectly contribute to photoreceptor cell survival as well. Because both RPE and photoreceptor cells die in retinal degenerations, our findings contribute to the understanding of retinal cell survival signaling and potentially to the development of new therapeutic strategies.age-related macular degeneration ͉ docosanoids ͉ neurodegeneration ͉ neuroprotection ͉ Bcl-2 proteins

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Section: Discussionmentioning

confidence: 57%

Neuroprotectin D1: A docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress

Mukherjee

Marcheselli

Serhan

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

693

690

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“…Furthermore, it could be demonstrated that nitric oxide protects keratinocytes and endothelial cells from UVA-induced apoptosis, probably via upregulation of Bcl-2 (56). Similarly, extracellular matrixmediated protection of retinal pigment epithelial cells from UVA-induced apoptosis was found to correlate with Bcl-2 protein expression (57). In addition, skin explants from Bcl-2 deficient mice exhibited a higher number of SC following exposure to UVB (58).…”

Section: Participation Of the Bcl-2 Protein Family And Mitochondrial mentioning

confidence: 85%

Molecular mechanisms of UV‐induced apoptosis

Kulms

Schwarz

2000

Photoderm Photoimm Photomed

284

206

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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

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“…Studies from our laboratory indicate that treatment of MCF-7 cells with NCS results in downregulated expression of Bcl-2 and up-regulated expression of its proapoptotic analog, Bax (Liang et al, 2001). The resulting decrease in the Bcl-2/Bax ratio has been shown in other systems to trigger the release of cytochrome c from the mitochondria (Nakatsuka et al, 2000), and to thereby induce apoptosis (Putcha et al, 1999;Liang et al, 2000). Modulation of the Bcl-2/Bax ratio perhaps represents an alternative mechanism of potentiation of apoptosis in cells lacking caspase 3.…”

Section: Discussionmentioning

confidence: 99%

Role of Caspase 3-Dependent Bcl-2 Cleavage in Potentiation of Apoptosis by Bcl-2

et al. 2002

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Previous studies from our laboratory have demonstrated that Bcl-2 has a proapoptotic effect on neocarzinostatin (NCS)-treated PC12 pheochromocytoma cells. In the present study, we examine the mechanisms of this effect and demonstrate its relevance for the in vivo situation. Four hours after NCS treatment, a 23-kDa cleavage product of Bcl-2 was detected in whole cell lysates of bcl-2-transfected PC12 cells. In contrast, bcl-2 transfection protected PC12 cells from cisplatin-induced apoptosis, and cisplatin treatment did not result in Bcl-2 cleavage. Similarly, Bcl-2 cleavage did not occur and Bcl-2-mediated protection from, rather than potentiation of apoptosis was observed after NCS treatment of MCF-7 breast cancer cells.The caspase 3-specific inhibitor Ac-DEVD-CHO prevented Bcl-2 cleavage and attenuated NCS-induced apoptosis in bcl-2-transfected PC12 cells, whereas it had no effect on NCSinduced apoptosis in mock-transfected PC12 cells. Furthermore, MCF-7 cells do not express caspase 3, a finding in concert with the lack of Bcl-2 cleavage in this line. In in vivo experiments, xenografts of bcl-2-transfected PC12 cells were more susceptible to NCS toxicity than were xenografts of mock-transfected PC12 cells. Caspase 3-mediated Bcl-2 cleavage therefore plays an important role in the potentiation by Bcl-2 of NCS-induced apoptosis.

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Bcl-2, Bax, and c-Fos expression correlates to RPE cell apoptosis induced by UV-light and daunorubicin

Cited by 30 publications

References 30 publications

Neuroprotectin D1: A docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress

Neuroprotectin D1: A docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress

Molecular mechanisms of UV‐induced apoptosis

Role of Caspase 3-Dependent Bcl-2 Cleavage in Potentiation of Apoptosis by Bcl-2

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