Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conventional photodynamic therapy (PDT) utilizes light-absorbing compounds that have anti-cancer activity upon visible light irradiation. PDT has also been utilized for the treatment of certain immune conditions. To further understand the action of PDT upon immune cells, DBA/2 mouse thymocytes were treated with the photosensitizer benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) and/or an apoptosis-inducing anti-Fas (APO-1, CD95) monoclonal antibody. Nanomolar levels of BPD-MA in combination with nonthermal visible light irradiation rapidly induced apoptosis as gauged by DNA fragmentation assays. Thymocytes were modestly more sensitive to PDT-induced apoptosis than mature splenic T cells. BPD-MA and light or the anti-Fas antibody decreased CD4(+)CD8(+) cell numbers while relatively sparing CD4(-)CD8(-), CD4(+)CD8(-), and CD4(-)CD8(+) thymocytes. In combination, anti-Fas antibody and PDT augmented activity levels of the apoptosis-related protease caspase-3, cleavage of the caspase-3 substrate poly(ADP) polymerase, and the proportion of cells exhibiting DNA fragmentation and further impacted CD4(+)CD8(+) thymocyte survival. Although CD4(+)CD8(+) thymocytes had the greatest sensitivity to photodynamic depletion, BPD-MA was taken up by the other major thymocyte subsets with equal or greater avidity. Since CD4(+)CD8(+) thymocytes are selectively impacted by PDT and anti-Fas antibody can act in concert with PDT to further cytotoxicity, thymocytes may be useful for the identification of factors that govern immune cell susceptibility to this form of phototherapy.
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PMID:Selective depletion of a thymocyte subset in vitro with an immunomodulatory photosensitizer. 1022 10

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.
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PMID:Bcl-2 overexpression blocks caspase activation and downstream apoptotic events instigated by photodynamic therapy. 1040 99

Caspases have been shown to play a crucial role in apoptosis induced by various deleterious and physiologic stimuli. In this study, we show for the first time that photodynamic therapy (PDT), using benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) as the photosensitizer, induces the complete cleavage and subsequent activation of caspase-3 (CPP32/Yama/Apopain) but not caspase-1 (ICE) in human promyelocytic leukemia HL-60 cells. Poly(ADP-ribose) polymerase (PARP) and the catalytic subunit of DNA dependent protein kinase (DNA PK(CS)) were cleaved within 60 min of light activation of BPD-MA. The general caspase inhibitor Z-Asp-2,6 dichlorobenzoyloxymethylketone (Z-Asp-DCB) blocked PARP cleavage while the serine protease inhibitors 3,4-dichloroisocoumarin (DCI) and N-tosyl-lysyl chloromethyl ketone (TLCK) blocked the cleavage of caspase-3 suggesting that they act upstream of caspase-3 activation. All three inhibitors were able to block DNA fragmentation that was induced by treatment with BPD-MA followed by light application. These studies demonstrate that protease activity, particularly that of caspase-3, is triggered in HL-60 cells treated with lethal levels of BPD-MA and visible light.
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PMID:Photodynamic therapy induces caspase-3 activation in HL-60 cells. 1455 76