scholarly journals Evidence for Agrobacterium-Induced Apoptosis in Maize Cells

2000 ◽  
Vol 13 (6) ◽  
pp. 649-657 ◽  
Author(s):  
Geneviève Hansen
Keyword(s):  
Cell Death ◽  
Dna Cleavage ◽  
Morphological Changes ◽  
Plant Cells ◽  
Plant Tissues ◽  
Apoptotic Pathway ◽  
Dicotyledonous Plant ◽  
Apoptotic Genes ◽  
Baculovirus P35 ◽  
Induced Apoptosis

Agrobacterium spp. can genetically transform most dicotyledonous plant cells whereas many monocot species are recalcitrant to Agrobacterium-mediated transformation. One major obstacle is that co-cultivation of Agrobacterium spp. with plant tissues often results in cell death. Report here is that, in maize tissues, this process resembles apoptosis, with characteristic DNA cleavage into oligonucleosomal fragments and morphological changes. Two anti-apoptotic genes from baculovirus, p35 and iap, had the ability to prevent the onset of apoptosis triggered by Agrobacterium spp. in maize tissues. p35 is reported to act as a direct inhibitor of a certain class of proteases (caspase) whereas iap may act upstream to prevent their activation. This evidence raises the possibility that caspase-like proteases may also be involved in the apoptotic pathway in plant cells.

4-Acetyl-12,13-Epoxyl-9-Trichothecene-3,15-Diol from Isaria japonica Mediates Apoptosis of Rat Bladder Carcinoma NBT-II Cells by Decreasing Anti-apoptotic Bcl-2 Expression and Increasing Pro-apoptotic Bax Expression

2004 ◽  
Vol 32 (03) ◽  
pp. 377-387 ◽  
Author(s):  
Hyung-Jin Kim ◽  
Seon Il Jang ◽  
Young-Jun Kim ◽  
Hyun-Ock Pae ◽  
Hae-Young Won ◽  
...  
Keyword(s):  
Cell Death ◽  
Bladder Carcinoma ◽  
Cytotoxic Effect ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Morphological Changes ◽  
Rat Bladder ◽  
Apoptotic Protein ◽  
Induction Of Apoptosis ◽  
Induced Apoptosis

We studied the effect of 4-acetyl-12,13-epoxyl-9-trichothecene-3,15-diol (AETD) isolated from Isaria japonica, one of the most popular Chinese fungal medicines, on the induction of apoptosis in rat bladder carcinoma NBT-II cells. AETD was cytotoxic to NBT-II cells, and this cytotoxic effect appears to be attributed to its induction of apoptotic cell death, as AETD induced nuclear morphological changes and internucleosomal DNA fragmentation, and increased the proportion of hypodiploid cells and activity of caspase-3. AETD treatment also decreased the expression of the anti-apoptotic protein Bcl-2 and increased the expression of the pro-apoptotic protein Bax. These results provide important information in understanding the mechanism(s) of AETD-induced apoptosis.

Mechanisms of death induced by cisplatin in proximal tubular epithelial cells: apoptosis vs. necrosis

1996 ◽  
Vol 270 (4) ◽  
pp. F700-F708 ◽  
Author(s):  
W. Lieberthal ◽  
V. Triaca ◽  
J. Levine
Keyword(s):  
Cell Death ◽  
Dna Cleavage ◽  
Primary Cultures ◽  
Cell Monolayer ◽  
Membrane Integrity ◽  
Ladder Pattern ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
High Concentrations ◽  
Induced Apoptosis

We have examined the mechanisms of cell death induced by cisplatin in primary cultures of mouse proximal tubular cells. High concentrations of cisplatin (800 microM) led to necrotic cell death over a few hours. Much lower concentrations of cisplatin (8 microM) led to apoptosis, which caused loss of the cell monolayer over several days. Necrosis was characterized by a cytosolic swelling and early loss of plasma membrane integrity. In contrast, early features of cells undergoing apoptosis included cell shrinkage and loss of attachment to the monolayers. Nuclear chromatin became condensed and fragmented in apoptosing cells. These features were absent in necrotic cells. DNA electrophoresis of cells exposed to 800 microM cisplatin yielded a "smear" pattern, due to random DNA degradation. In contrast, the DNA of apoptosing cells demonstrated a "ladder" pattern resulting from internucleosomal DNA cleavage. Antioxidants delayed cisplatin-induced apoptosis but not necrosis. Thus the mechanism of cell death induced by cisplatin is concentration dependent. Reactive oxygen species play a role in mediating apoptosis but not necrosis induced by cisplatin.

Identification of apoptotic genes mediating TGF-β/Smad3-induced cell death in intestinal epithelial cells using a genomic approach

2007 ◽  
Vol 292 (1) ◽  
pp. G28-G38 ◽  
Author(s):  
Yanna Cao ◽  
Lu Chen ◽  
Weili Zhang ◽  
Yan Liu ◽  
Harry T. Papaconstantinou ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Intestinal Epithelial ◽  
Cytochrome C Release ◽  
Apoptotic Pathway ◽  
Genomic Approach ◽  
Apoptotic Genes ◽  
Induced Apoptosis

Transforming growth factor (TGF)-β-dependent apoptosis is important in the elimination of damaged or abnormal cells from normal tissues in vivo. Previously, we have shown that TGF-β inhibits the growth of rat intestinal epithelial (RIE)-1 cells. However, RIE-1 cells are relatively resistant to TGF-β-induced apoptosis due to a low endogenous Smad3-to-Akt ratio. Overexpression of Smad3 sensitizes RIE-1 cells (RIE-1/Smad3) to TGF-β-induced apoptosis by altering the Smad3-to-Akt ratio in favor of apoptosis. In this study, we utilized a genomic approach to identify potential downstream target genes that are regulated by TGF-β/Smad3. Total RNA samples were analyzed using Affymetrix oligonucleotide microarrays. We found that TGF-β regulated 518 probe sets corresponding to its target genes. Interestingly, among the known apoptotic genes included in the microarray analyses, only caspase-3 was induced, which was confirmed by real-time RT-PCR. Furthermore, TGF-β activated caspase-3 through protein cleavage. Upstream of caspase-3, TGF-β induced mitochondrial depolarization, cytochrome c release, and cleavage of caspase-9, which suggests that the intrinsic apoptotic pathway mediates TGF-β-induced apoptosis in RIE-1/Smad3 cells.

scholarly journals Cell death in the avian blastoderm: resistance to stress-induced apoptosis and expression of anti-apoptotic genes

1998 ◽  
Vol 5 (6) ◽  
pp. 529-538 ◽  
Author(s):  
Stephen E Bloom ◽  
Donna E Muscarella ◽  
Mitchell Y Lee ◽  
Melissa Rachlinski
Keyword(s):  
Cell Death ◽  
Resistance To Stress ◽  
Apoptotic Genes ◽  
Induced Apoptosis

A Novel Ring-Substituted Diindolylmethane 1,1-bis [3′-(5-methoxyindolyl)]-1-(p-t-butylphenyl) Methane Abrogates ERK Activation and Induces Apoptosis in Acute Myeloid Leukemia (AML).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3399-3399
Author(s):  
Rooha Contractor ◽  
Ismael J. Samudio ◽  
Zeev Estrov ◽  
David Harris ◽  
James A. McCubrey ◽  
...  
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Caspase 9 ◽  
Apoptotic Pathway ◽  
Erk Activation ◽  
New Class ◽  
Induced Apoptosis ◽  
Extracellular Regulated Kinase

Abstract We investigated the antileukemic activity and molecular mechanisms of action of a newly synthesized ring-substituted diindolylmethane (DIM) derivative, named, 1,1-bis [3′-(5-methoxyindolyl)]-1-(p-t-butylphenyl) methane (DIM #34), in myeloid leukemic cells. DIM #34 inhibited leukemic cell growth via induction of apoptosis. DIM #34 inhibited clonogenic growth and induced apoptosis of AML CD34+ progenitor cells but spared normal progenitors. DIM #34 induced loss of mitochondrial membrane potential, which was accompanied by the release of cytochrome c into the cytosol and early cleavage of caspase-9 followed by the cleavage of caspases -8, and -3. Bcl-2 overexpression and caspase-9-deficient cells were partially protected against DIM #34-induced apoptosis, suggesting activation of the intrinsic apoptotic pathway. DIM #34 induced Bax cleavage, and Bax knockout cells were partially resistant to cell death. Furthermore, DIM #34 transiently inhibited the phosphorylation and the activity of the extracellular-regulated kinase (ERK) and abrogated Bcl-2 phosphorylation. Because other methylene substituted DIM analogs transactivate the nuclear receptor PPARγ, we studied the role of PPARγ in apoptosis induction. Although the co-treatment of cells with a selective PPARγ antagonist T007, and a low dose of DIM #34 partially diminished apoptosis, apoptosis was not inhibited at higher concentrations of DIM #34, suggesting the involvement of both, receptor-dependent and independent mechanisms. Co-treatment with RXR- and RAR-ligands enhanced DIM #34-induced cell death. Together, these findings showed that substituted DIMs represent a new class of compounds that selectively induce apoptosis in AML cells through interference with ERK and activation of PPARγ signaling pathways.

scholarly journals GDP dissociation inhibitor D4-GDI (Rho-GDI 2), but not the homologous Rho-GDI 1, is cleaved by caspase-3 during drug-induced apoptosis

2000 ◽  
Vol 346 (3) ◽  
pp. 777-783 ◽  
Author(s):  
Frank ESSMANN ◽  
Thomas WIEDER ◽  
Albrecht OTTO ◽  
Eva-Christina MÜLLER ◽  
Bernd DÖRKEN ◽  
...  
Keyword(s):  
Cell Death ◽  
Rho Gtpases ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Morphological Changes ◽  
Drug Induced ◽  
Two Dimensional Gel Electrophoresis ◽  
Homologous Protein ◽  
Induced Apoptosis ◽  
Gdp Dissociation Inhibitor

Different cytotoxic drugs induce cell death by activating the apoptotic programme; a family of cysteinyl aspartate proteases named caspases has been shown to be involved in the initiation as well as the execution of this kind of cell death. In the present study, cleavage of D4-GDI (Rho-GDI 2), an abundant haemopoietic-cell GDP dissociation inhibitor for the Ras-related Rho family GTPases, was demonstrated after treatment of BJAB Burkitt-like lymphoma cells with taxol or epirubicin. The cleavage of D4-GDI occurred simultaneously with the activation of caspase-3 but preceded DNA fragmentation and the morphological changes associated with apoptotic cell death. By using high-resolution two-dimensional gel electrophoresis it was shown that this cleavage is specific: whereas the level of the homologous protein Rho-GDI 1 was not significantly altered during drug-induced apoptosis and in cytochrome c/dATP-activated cellular extracts, D4-GDI disappeared owing to proteolytic cleavage. Inhibitor experiments with Z-DEVD-fmk (in which Z stands for benzyloxycarbonyl and fmk for fluoromethyl ketone) and microsequencing of the D4-GDI fragment revealed that this occurs at the caspase-3 cleavage site. Our results strongly suggest the differential regulation of the homologous GDP dissociation inhibitors Rho-GDI 1 and D4-GDI during drug-induced apoptosis by proteolysis mediated by caspase-3 but not by caspase-1. Owing to their crucial role as modulators of Rho GTPases, this might in turn have a significant impact on the mechanisms that induce the cytoskeletal and morphological changes in apoptotic cells.

scholarly journals Fas Induces Cytoplasmic Apoptotic Responses and Activation of the MKK7-JNK/SAPK and MKK6-p38 Pathways Independent of CPP32-like Proteases

1997 ◽  
Vol 139 (4) ◽  
pp. 1005-1015 ◽  
Author(s):  
Fumiko Toyoshima ◽  
Tetsuo Moriguchi ◽  
Eisuke Nishida
Keyword(s):  
Cell Death ◽  
Dna Fragmentation ◽  
Morphological Changes ◽  
Chromatin Condensation ◽  
Cysteine Proteases ◽  
Cellular Responses ◽  
Jurkat Cells ◽  
Mitogen Activated Protein Kinase ◽  
Fas Signaling ◽  
Induced Apoptosis

IL-1β converting enzyme (ICE) family cysteine proteases are subdivided into three groups; ICE-, CPP32-, and Ich-1–like proteases. In Fas-induced apoptosis, activation of ICE-like proteases is followed by activation of CPP32-like proteases which is thought to be essential for execution of the cell death. It was recently reported that two subfamily members of the mitogen-activated protein kinase superfamily, JNK/SAPK and p38, are activated during Fas-induced apoptosis. Here, we have shown that MKK7, but not SEK1/ MKK4, is activated by Fas as an activator for JNK/ SAPK and that MKK6 is a major activator for p38 in Fas signaling. Then, to dissect various cellular responses induced by Fas, we used several peptide inhibitors for ICE family proteases in Fas-treated Jurkat cells and KB cells. While Z-VAD-FK which inhibited almost all the Fas-induced cellular responses blocked the activation of JNK/SAPK and p38, Ac-DEVD-CHO and Z-DEVD-FK, specific inhibitors for CPP32-like proteases, which inhibited the Fas-induced chromatin condensation and DNA fragmentation did not block the activation of JNK/SAPK and p38. Interestingly, these DEVD-type inhibitors did not block the Fas-induced morphological changes (cell shrinkage and surface blebbing), induction of Apo2.7 antigen, or the cell death (as assessed by the dye exclusion ability). These results suggest that the Fas-induced activation of the JNK/SAPK and p38 signaling pathways does not require CPP32-like proteases and that CPP32-like proteases, although essential for apoptotic nuclear events (such as chromatin condensation and DNA fragmentation), are not required for other apoptotic events in the cytoplasm or the cell death itself. Thus, the Fas signaling pathway diverges into multiple, separate processes, each of which may be responsible for part of the apoptotic cellular responses.

Caspase-3 Activity and Carbonyl Cyanide m-Chlorophenylhydrazone-induced Apoptosis in HL-60 cells

2001 ◽  
Vol 29 (3) ◽  
pp. 243-249 ◽  
Author(s):  
Petr Mlejnek
Keyword(s):  
Cell Death ◽  
Dna Cleavage ◽  
Caspase 3 ◽  
Chromatin Condensation ◽  
Experimental System ◽  
Apoptotic Bodies ◽  
Nucleosomal Dna ◽  
Carbonyl Cyanide ◽  
Induced Apoptosis ◽  
Fluoromethyl Ketone

The role of caspase proteases in carbonyl cyanide m-chlorophenylhydrazone (CCCP)-induced apoptosis of human promyelocytic HL-60 cells was examined. Treatment of HL-60 cells with micromolar concentrations of CCCP resulted in cell death, with typical apoptotic features such as chromatin condensation, formation of apoptotic bodies, nucleosomal fragmentation of DNA and a distinct increase in caspase-3 activity. The results, however, indicated that full caspase-3 inhibition by the selective inhibitor N-benzyloxycarbonyl-Asp-Glu-Val-Asp fluoromethyl ketone (Z-DEVD-FMK) did not prevent cell death, nor did it affect the manifestation of apoptotic hallmarks, including apoptotic bodies formation and nucleosomal DNA fragmentation. The only distinct effect that Z-DEVD-FMK exhibited was to retard the disruption of the plasma membrane. We therefore assume that caspase-3 activity itself is not essential for the manifestation of apoptotic features mentioned above. Similarly, the pan-specific caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD-FMK) did not prevent cell death. On the contrary, Z-VAD-FMK completely prevented DNA cleavage and apoptotic body formation, but it failed to completely counteract chromatin condensation. Thus, in the presence of Z-VAD-FMK, application of CCCP concentrations that otherwise induced apoptosis, resulted in the appearance of two morphologically different groups of dead cells with intact DNA. The first group included cells with necrotic-like nuclear morphology, and therefore could be taken as being “truly” necrotic in nature, because they had intact DNA. The cells of the second group formed small single-spherical nuclei with condensed chromatin. In spite of having intact DNA, they could not be taken as “truly” necrotic cells. It is evident that in the experimental system, caspase proteases play an essential role in the formation of apoptotic bodies and in the cleavage of nucleosomal DNA, but not in the condensation of chromatin. Therefore, it is likely that the choice between cell death modalities is not solely a matter of the caspase proteases present.

A Novel Inosine Monophosphate Dehydrogenase Inhibitor VX-944 Overcomes Conventional Drug-Resistance in Multiple Mueloma Cells in the Bone Marrow Microenvironment.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2468-2468
Author(s):  
Kenji Ishitsuka ◽  
Teru Hideshima ◽  
Makoto Hamasaki ◽  
Raje Noopur ◽  
Kumar Shaji ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Death ◽  
De Novo ◽  
Parp Cleavage ◽  
Inosine Monophosphate Dehydrogenase ◽  
Apoptotic Pathway ◽  
Inosine Monophosphate ◽  
Induced Apoptosis ◽  
Monophosphate Dehydrogenase

Abstract Inosine monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme required for the de novo synthesis of guanine nucleotides from IMP. VX-944 (Vertex Pharmaceuticals, Cambridge, MA) is a small molecule, selective, uncompetitive novel inhibitor directed against human IMPDH enzyme. IMPDH inhibitors have been demonstrated to induce growth arrest, and extensively investigated as immunosuppressants. Here we show that VX-944 inhibits growth of human multiple myeloma (MM) cell lines, including those resistant to conventional agents, via induction of apoptosis and S phase arrest in vitro. Interleukin-6, insulin-like growth factor-1, or co-culture with bone marrow stromal cells (BMSCs), do not protect against VX-944-induced MM cell growth inhibition. We next delineated the molecular mechanism of VX-944-induced MM cell death in the MM.1S human MM cell line. VX-944 induced apoptosis in MM.1S cells, confirmed by PARP cleavage as well as flow cytometric detection of the mitochondrial membrane protein 7A6 and TdT-mediated dUTP nick-end labelling (TUNEL) positive cells, without significant cleavage of caspases 3, 8 and 9. While the pan-caspase inhibitor z-VAD-fmk did not inhibit the VX-944-induced apoptosis and cell death suggesting that VX-944 triggers apoptosis in MM1.S cells primarily via caspase-independent pathway. Importantly, VX-944 augments the cytotoxicity of doxorubicin, melphalan and bortezomib, all of which activate caspases in MM cells and induce apoptosis, even in the presence of BMSCs. Taken together, our data demonstrate non-caspase-dependent apoptotic pathway triggered by VX-944 thereby providing a rationale to enhance MM cell cytotoxicity by combining this agent with conventional and/or novel agents which trigger caspase activation. Our ongoing studies are delineating the mechanisms whereby VX-944 induces MM cell apoptosis.

Programmed Cell Death (Apoptosis) and Cancer Chemotherapy

1996 ◽  
Vol 3 (4) ◽  
pp. 303-309 ◽  
Author(s):  
Samuel R. Denmeade ◽  
John T. Isaacs
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Morphological Changes ◽  
Malignant Cell ◽  
Death Process ◽  
Tumor Resistance ◽  
Apoptotic Pathway ◽  
Exogenous Agents ◽  
Specific Alteration ◽  
Energy Dependent

Background Programmed cell death involves a genetic reprogramming of the cell to promote an energy-dependent cascade of biochemical and morphological changes within the cell that result in its death and elimination. Methods The regulations and mechanisms of programmed cell death are reviewed with an emphasis on how derangement of this mechanism may be involved in modulating responsiveness to chemotherapy. Results Activation of this programmed death process is controlled by a series of endogenous cell-type-specific signals. In addition, a variety of exogenous cell-damaging treatments (eg, radiation, chemicals, and viruses) and most chemotherapeutic drugs can activate this pathway if sufficient injury to the cell occurs. Resistance to chemotherapy can involve alterations in the ability of a malignant cell to activate the programmed cell death (apoptotic) pathway when damaged by these exogenous agents. Conclusion The most important determinant of tumor resistance may be a generalized resistance to induction of programmed cell death rather than resistance based on specific alteration in drug/target interactions.

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