Caspase-dependent and -independent mechanisms in apoptosis induced by hydroquinone and catechol metabolites of remoxipride in HL-60 cells

Inayat-Hussain, Salmaan H.; McGuinness, Susan M.; Lundström, Jan O.; Ross, David

doi:10.1016/s0009-2797(00)00188-5

Cited by 15 publications

(12 citation statements)

References 41 publications

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“…ZVAD‐fmk treatment has also been shown to generate p19 and p20, which are partially processed fragments of p17 at two different cleavage sites in its N‐terminus (Eldering et al, 2004). In addition, there are a small number of reports that show a slight MW increase in p17 after zVAD‐fmk treatment, which is in line with our own data shown in this report (Inayat‐Hussain et al, 2000; Thibodeau et al, 2003). Although caspase‐3 has been indicated in most reports to possess only a single cleavage site at Asp175 between p17 and p12 in contrast to two sites that generate a 2 kDa linker for caspase‐1 (Cohen, 1997; Shi, 2002), there are a number of reports that show an additional cleavage site at Asp179 or Asp180 (Fuentes‐Prior and Salvesen, 2004; protein accession # NP 004337).…”

Section: Discussionsupporting

confidence: 92%

Hypoxia‐induced apoptosis and tube breakdown are regulated by p38 MAPK but not by caspase cascade in an in vitro capillary model composed of human endothelial cells

Ohta

Eguchi

Suzuki

et al. 2007

Journal Cellular Physiology

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In order to improve medical treatment of ischemic injury such as myocardial infarction, it is important to elucidate hypoxia-induced changes to endothelial cells. An in vitro blood vessel model, in which HUVECs are stimulated to form a network of capillary-like tubes, was used to analyze hypoxia-induced morphological and biochemical changes. When exposed to hypoxia, the network of capillary tubes broke down into small clusters. This tube breakdown was accompanied by chromatin condensation and cell nuclear fragmentation, morphological markers of apoptosis, and activation of two apoptotic signals, caspase-3 and p38. We investigated what roles caspase cascade and p38 play in hypoxia-induced apoptosis and tube breakdown by using zVAD-fmk and SB203580, specific inhibitors of these two apoptotic signals, respectively. Chromatin condensation and cell nuclear fragmentation and tube breakdown were effectively inhibited by SB203580, but not by zVAD-fmk. SB203580 caused dephosphorylation of p38, which indicates that p38 was autophosphorylated. Inhibition by zVAD-fmk caused slight MW increase in p17 and emergence of p19, which indicates that the inhibitor caused partial processing of caspase-3. Inhibition of p38 suppressed activation of caspase-3 but not vice versa. In addition, these two inhibitors were shown to differentially inhibit cleavage of so-called caspase substrates. SB203580 inhibited cleavage of PARP and lamin A/C, while zVAD-fmk inhibited cleavage of lamin A/C but not that of PARP. Taken together, these results show that p38 is located upstream of caspase cascade and that, although caspase-3 is activated, a p38-regulated caspase-independent pathway is crucial for the execution of hypoxia-induced apoptosis and tube breakdown.

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Section: Discussionsupporting

confidence: 92%

Hypoxia‐induced apoptosis and tube breakdown are regulated by p38 MAPK but not by caspase cascade in an in vitro capillary model composed of human endothelial cells

Ohta

Eguchi

Suzuki

et al. 2007

Journal Cellular Physiology

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“…4 c ) 15. In fact, it has been reported that z‐VAD blocks caspase‐3 processing and activity,48 and that RGD‐containing peptides induce auto‐processing and activity of pro‐caspase‐3, that contains an RGD‐binding motif near its processing site 49. Considering these data, we suppose that z‐VAD, inhibiting caspase‐3, inhibits RGD binding to pro‐caspase‐3, leaving thus the RGD‐binding motif more accessible to GrB.…”

Section: Resultsmentioning

confidence: 99%

Granzyme B is expressed in urothelial carcinoma and promotes cancer cell invasion

D'Eliseo

Pisu

Romano

et al. 2010

Intl Journal of Cancer

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Granzyme B (GrB) is a serine proteinase known to be expressed by cytotoxic lymphocytes and to induce, in presence of perforin (Pf), apoptosis in target cells. Recently, GrB expression has been shown (often in absence of Pf) in nonlymphoid cells, but its function is not defined. In our study, we investigated GrB and Pf expression in bladder cancer cell lines and in urothelial carcinoma (UC) tissues by reverse transcription-polymerase chain reaction (RT-PCR), Western blot, ELISA, immunofluorescence and immunohistochemistry. We also assessed the function of GrB in UC cells; the in vitro function of GrB was examined by loss-of-function experiments. Our results revealed that GrB is expressed, in absence of Pf, in UC cells. Significant differences were found between GrB expression and both increasing pathological tumor spreading and high-grade vs. low-grade pTa tumors. Notably, GrB in UC tissues was concentrated at the cancer invasion front and was expressed in neoplastic cells undergoing epithelial-mesenchymal transition, a key event in carcinoma invasion. Indeed, GrB-positive cells also expressed Snail, N-cadherin or were negative for E-cadherin. GrB expressed in tumor cell lines was enzymatically active and capable of vitronectin cleavage, implying extracellular matrix (ECM) remodeling by GrB. Inhibition of GrB activity or Stealth RNA interference-mediated GrB gene silencing markedly suppressed bladder cancer cell invasion through matrigel. This data provides the first evidence for a role of GrB in promoting cancer cell invasion. Taken together, our findings suggest that GrB, via ECM degradation, contributes to the establishment of the UC invasive phenotype.

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“…In some experiments, the cells were preincubated for 1 h with ZVAD (100 μM), ZVDVAD (50 μM), NAC (5 mM), ZB4 (1 μg/mL), or NOK-1 (1 μg/mL) prior to HQ treatment. In experiments using the remoxipride metabolites, cells were treated with 100 μM NCQ344 and 100 μM NCQ436 for 14 h. Apoptosis was assessed using flow cytometry essentially as described previously using the annexin-V/propidium iodide (PI) and DIOC 6 (3) methods ( , ). Cells (0.5 × 10 6 ) were resuspended in media binding buffer containing annexin-V and incubated for 12 min in the dark at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Intrinsic Pathway of Hydroquinone Induced Apoptosis Occurs via Both Caspase-Dependent and Caspase-Independent Mechanisms

Inayat-Hussain

Ross

2005

Chem. Res. Toxicol.

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The role of mitochondria and apical caspases in apoptosis induced by the benzene metabolite hydroquinone (HQ) remains to be elucidated. Here, we investigated the involvement of mitochondria and activation of the apical caspases-8 and -9 in HQ induced apoptosis in myeloperoxidase (MPO)-rich HL-60 and MPO-deficient Jurkat T cells. Treatment of HL-60 and Jurkat cells with HQ resulted in apoptosis as assessed by phosphatidyl serine (PS) exposure, loss of mitochondrial transmembrane potential (MTP), release of cytochrome c, and processing of apical caspases-8 and -9 and executioner caspase-3. In HQ-treated HL-60 cells, pretreatment with the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (ZVAD), which did not inhibit PS exposure, also failed to abrogate the loss of MTP and release of cytochrome c. However, complete processing of caspase-9 was inhibited in the presence of ZVAD. In marked contrast, in HQ-treated Jurkat cells, ZVAD significantly abrogated PS exposure, loss of MTP, and caspase-9 processing but not release of cytochrome c. Although ZVAD-sensitive caspase-8 processing occurred in both cell types, pretreatment with either fas-receptor blocking ZB4 or fas-ligand NOK1 neutralizing antibodies did not inhibit HQ-induced apoptosis. In conclusion, our results demonstrate that HQ induced apoptosis in Jurkat cells occurs via a ZVAD-inhibitable, caspase-dependent process, while in HL-60 cells, apoptosis occurs predominantly via caspase-independent mechanisms. Our results emphasize that both caspase-dependent and independent mechanisms should be considered in the intrinsic apoptotic pathway induced by HQ.

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Caspase-dependent and -independent mechanisms in apoptosis induced by hydroquinone and catechol metabolites of remoxipride in HL-60 cells

Cited by 15 publications

References 41 publications

Hypoxia‐induced apoptosis and tube breakdown are regulated by p38 MAPK but not by caspase cascade in an in vitro capillary model composed of human endothelial cells

Hypoxia‐induced apoptosis and tube breakdown are regulated by p38 MAPK but not by caspase cascade in an in vitro capillary model composed of human endothelial cells

Granzyme B is expressed in urothelial carcinoma and promotes cancer cell invasion

Intrinsic Pathway of Hydroquinone Induced Apoptosis Occurs via Both Caspase-Dependent and Caspase-Independent Mechanisms

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