Overexpression of Bcl‐X<sub>L</sub> prevents caspase‐3‐mediated activation of DNA fragmentation factor (DFF) produced by treatment with the photochemotherapeutic agent BPD‐MA

Granville, David J.; Jiang, Huijun; An, Mary T; Levy, Julia G.; McManus, Bruce M.; Hunt, David W. C.

doi:10.1016/s0014-5793(97)01616-5

Cited by 42 publications

(17 citation statements)

References 22 publications

(51 reference statements)

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“…In this case, Bcl-2 overexpression prevented pro-caspase-3 and -6 cleavage, proteolysis of PARP and formation of hypodiploid DNA [77]. Overexpression of Bcl-x L in HL-60 cells also prevented PDT-induced cleavage of pro-caspase-3 and DNA fragmentation [76]. Enforced expression of Bcl-2 also delayed PDT-induced apoptotic death in a rat/mouse T cell hybridoma (PC60R1R2) sensitized with hypericin, by delaying cytochrome C release, pro-caspase-3 activation and PARP cleavage [68], and similar findings were reported in Jurkat cells photosensitized with hypericin [69].…”

Section: Role Of the Bcl-2 Family Of Proteins In Pdtmentioning

confidence: 86%

“…Also, expression of CrmA did not affect the kinetics of cytochrome C release Jurkat human lymphoma T cells [295] and procaspase-3 cleavage in a rat/mouse T cell hybridoma sensitized with hypericin [68], suggesting that caspase-8 does not play a major role in the demise process in this model. The activation of caspases in photosensitized cells leads to the cleavage of a number of other cell proteins, including Bap-31 (shuttle protein between the ER and the intermediate compartment and/or Golgi complex [71]), DNA-dependent protein kinase (catalytic subunit) (DNA-PK CS [75]), ICAD (inhibitor of caspase activated DNAse); prevents DNA fragmentation via binding to caspase-activated deoxyribonuclease [76]), focal adhesion kinase (FAK, a kinase involved in the regulation of cell adhesion [73]), lamins (structural components of the nuclear envelope [73]), PARP (poly(ADP-ribose) polymerase, a DNA repair enzyme [18,20,44,54,68,71,72,75,[77][78][79][80][81][82][83][84][85]) and Ras GTPase-activating protein (Ras-GAP, a negative regulator of the Ras signaling pathway [71]). DNA fragmentation in segments that are multiples of 180 -200 bp, another hallmark of apoptotic cell death [86], was also observed in PDT, using different cell types and sensitizers (Table 1).…”

Section: Role Of Caspases In Pdtmentioning

confidence: 99%

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Intracellular signaling mechanisms in photodynamic therapy

Almeida

Manadas

Carvalho

et al. 2004

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

242

292

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In photodynamic therapy (PDT) a sensitizer, light and oxygen are used to induce death of tumor cells and in the treatment of certain noncancerous conditions. Cell death in PDT may occur by apoptosis or by necrosis, depending on the sensitizer, on the PDT dose and on the cell genotype. Some sensitizers that have been used in PDT are accumulated in the mitochondria, and this may explain their efficiency in inducing apoptotic cell death, both in vitro and in vivo. In this review we will focus on the events that characterize apoptotic death in PDT and on the intracellular signaling events that are set in motion in photosensitized cells. Activation of phospholipases, changes in ceramide metabolism, a rise in the cytosolic free Ca 2 + concentration, stimulation of nitric oxide synthase (NOS), changes in protein phosphorylation and alterations in the activity of transcription factors and on gene expression have all been observed in PDT-treated cells. Although many of these metabolic reactions contribute to the demise process, some of them may antagonize cell death. Understanding the signaling mechanisms in PDT may provide means to modulate the PDT effects at the molecular level and potentiate its antitumor effectiveness. D

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Section: Role Of the Bcl-2 Family Of Proteins In Pdtmentioning

confidence: 86%

Section: Role Of Caspases In Pdtmentioning

confidence: 99%

Intracellular signaling mechanisms in photodynamic therapy

Almeida

Manadas

Carvalho

et al. 2004

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

242

292

View full text Add to dashboard Cite

show abstract

“…19 Briefly, fluorometric caspase-3 protease activity assays were performed in 96-well plates by incubating 50 L of cell lysate (10 g) with 100 L of reaction buffer (1% NP-40, 20 mmol/L Tris, pH 7.5, 137 mmol/L NaCl, 10% glycerol) and 100 mol/L of peptidic substrate Ac-DEVD-AMC (Calbiochem) at 37°C for 2 hours. The rate of caspase enzymatic hydrolysis was measured by release of AMC from the caspase substrate (emission of 460 nm on excitation at 380 nm).…”

Section: Caspase-3 Protease Activity Assaysmentioning

confidence: 99%

“…The rate of caspase enzymatic hydrolysis was measured by release of AMC from the caspase substrate (emission of 460 nm on excitation at 380 nm). 19 PARP cleavage analysis was performed by immunoblotting with PARP (Santa Cruz Biotechnology Inc). After incubation with horseradish peroxidase-labeled anti-goat-IgG antibody (1:5000) and detection with an enhanced chemiluminescence detection system (Amersham), bands were visualized by autoradiography.…”

Section: Caspase-3 Protease Activity Assaysmentioning

confidence: 99%

Attenuated Acute Cardiac Rejection in NOS2 −/− Recipients Correlates With Reduced Apoptosis

Koglin

Granville²,

Glysing-Jensen³

et al. 1999

Circulation

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Background-The mechanisms through which NOS2-mediated pathways regulate graft failure in acute cardiac rejection are ill defined. To determine whether apoptosis promoted by NOS2 may contribute, we used a heterotopic transplant model to study mouse cardiac allografts placed in recipients with targeted gene deletion of NOS2. Methods and Results-Using 5 different indexes of apoptosis, we showed that mouse cardiac allografts placed in NOS2 Ϫ/Ϫ recipients (nϭ7) had reduced apoptotic activity compared with those in NOS2 ϩ/ϩ controls (nϭ8). There were significantly fewer TUNEL-positive nuclei per high-powered field (PϽ0.01), less DNA fragmentation (antinucleosome ELISA; PϽ0.05), lower corrected transcript levels for caspase-1 and -3 ( 32 P reverse transcriptase-polymerase chain reaction; PϽ0.01), and reduced caspase-3 activity (cleavage of DEVD-pNA [PϽ0.001] and poly [ADP-ribose] polymerase) in grafts from NOS2 Ϫ/Ϫ recipients. This concordant reduction in apoptotic indexes paralleled the improved histological outcome of grafts transplanted into NOS2 Ϫ/Ϫ recipients (assessed as rejection scores; Pϭ0.012). To identify pathways controlled by NOS2, we compared intragraft transcript levels of potential triggers and regulators. Whereas Fas ligand/Fas and tumor necrosis factor (TNF)-␣/TNF receptor-1 levels were not altered by NOS2 deficiency, transcript levels for p53 were significantly lower in grafts from NOS2 Ϫ/Ϫ recipients, coinciding with a significant increase in the antiapoptotic Bcl-2/Bax balance and decrease in Bcl-X l levels. Conclusions-Using NOS2 knockout mice, we demonstrated that NOS2-mediated pathways can promote acute rejection, at least in part, by inducing apoptotic cell death. When NOS2 is present, p53 might control NOS2-mediated apoptosis by stimulating Bax and repressing Bcl-2 and Bcl-X l expression, which may activate the cell death program in the rejecting heart. (Circulation. 1999;99:836-842.)

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“…This endonuclease, CAD/CPAN, is only activated during apoptosis and is, therefore, believed to be responsible for DNA fragmentation (Halenbeck et al, 1998;Sakahira et al, 1998). We have shown that caspase-3-dependent cleavage of DFF occurs in PDTtreated HL-60 (Granville et al, 1998b) and HeLa cells (Carthy et al, 1998).…”

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confidence: 99%

Bcl-2 overexpression blocks caspase activation and downstream apoptotic events instigated by photodynamic therapy

Granville

Jiang

et al. 1998

Br J Cancer

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Treatment with the photosensitizer benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) followed by irradiation with visible light induces apoptosis in human acute myelogenous leukaemia HL-60 cells. Photoactivation of BPD-MA induces procaspase 3 (CPP32/Yama/apopain) and procaspase 6 (Mch2) cleavage into their proteolytically active subunits in these cells. The Bcl-2 proto-oncogene product has been shown to protect cells from a number of proapoptotic stimuli. In the present study, the influence of Bcl-2 overexpression on cellular resistance to photoactivation of BPD-MA was studied. Overexpression of Bcl-2 in HL-60 cells prevented apoptosis-related events including caspase 3 and 6 activation, poly(ADP-ribose) polymerase cleavage and the formation of hypodiploid DNA produced by BPD-MA (0–200 ng ml −1 ) and light. However, Bcl-2 overexpression was less effective at preventing cell death that occurred after photoactivation at high levels (50–100 ng ml −1 ) compared with lower doses (10–25 ng ml −1 ) of BPD-MA. These results indicate that caspase 3 and 6 activation and their regulation by Bcl-2 may play important roles in photodynamic therapy (PDT)-induced cell killing. © 1999 Cancer Research Campaign

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Overexpression of Bcl‐X_L prevents caspase‐3‐mediated activation of DNA fragmentation factor (DFF) produced by treatment with the photochemotherapeutic agent BPD‐MA

Cited by 42 publications

References 22 publications

Intracellular signaling mechanisms in photodynamic therapy

Intracellular signaling mechanisms in photodynamic therapy

Attenuated Acute Cardiac Rejection in NOS2 −/− Recipients Correlates With Reduced Apoptosis

Bcl-2 overexpression blocks caspase activation and downstream apoptotic events instigated by photodynamic therapy

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Overexpression of Bcl‐XL prevents caspase‐3‐mediated activation of DNA fragmentation factor (DFF) produced by treatment with the photochemotherapeutic agent BPD‐MA

Cited by 42 publications

References 22 publications

Intracellular signaling mechanisms in photodynamic therapy

Intracellular signaling mechanisms in photodynamic therapy

Attenuated Acute Cardiac Rejection in NOS2 −/− Recipients Correlates With Reduced Apoptosis

Bcl-2 overexpression blocks caspase activation and downstream apoptotic events instigated by photodynamic therapy

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Overexpression of Bcl‐X_L prevents caspase‐3‐mediated activation of DNA fragmentation factor (DFF) produced by treatment with the photochemotherapeutic agent BPD‐MA