The role of caspase family protease, caspase-3 on cisplatin-induced apoptosis in cisplatin-resistant A431 cell line

2000 ◽  
Vol 46 (3) ◽  
pp. 241-245 ◽  
Author(s):  
Hiroshi Mese ◽  
Akira Sasaki ◽  
Shuko Nakayama ◽  
Rafael E. Alcalde ◽  
Tomohiro Matsumura
Keyword(s):  
Cell Line ◽  
Caspase 3 ◽  
A431 Cell ◽  
Caspase Family ◽  
A431 Cell Line ◽  
Induced Apoptosis

Mechanism of cadmium induced apoptosis in human peripheral blood lymphocytes: The role of p53, Fas and Caspase-3

2013 ◽  
Vol 36 (3) ◽  
pp. 1033-1039 ◽  
Author(s):  
Abdullah H. Al-Assaf ◽  
Ali M. Alqahtani ◽  
Ali A. Alshatwi ◽  
Naveed A. Syed ◽  
Gowhar Shafi ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Caspase 3 ◽  
Human Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Blood Lymphocytes ◽  
Human Peripheral Blood Lymphocytes ◽  
Induced Apoptosis

scholarly journals UFL1 Alleviates LPS-Induced Apoptosis by Regulating the NF-κB Signaling Pathway in Bovine Ovarian Granulosa Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 260 ◽  
Author(s):  
Xinling Wang ◽  
Chengmin Li ◽  
Yiru Wang ◽  
Lian Li ◽  
Zhaoyu Han ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Granulosa Cells ◽  
Protein Concentration ◽  
Caspase 3 ◽  
Nuclear Factor Κb ◽  
Ovarian Granulosa Cells ◽  
Induced Apoptosis ◽  
Apoptosis Level ◽  
Lps Treatment

Ubiquitin-like modifier 1 ligating enzyme 1 (UFL1) is an E3 ligase of ubiquitin fold modifier 1 (UFM1), which can act together with its target protein to inhibit the apoptosis of cells. Lipopolysaccharides (LPS) can affect the ovarian health of female animals by affecting the apoptosis of ovarian granulosa cells. The physiological function of UFL1 on the apoptosis of bovine (ovarian) granulosa cells (bGCs) remains unclear; therefore, we focused on the modulating effect of UFL1 on the regulation of LPS-induced apoptosis in ovarian granulosa cells. Our study found that UFL1 was expressed in both the nucleus and cytoplasm of bGCs. The results here demonstrated that LPS caused a significant increase in the apoptosis level of bGCs in cows, and also dramatically increased the expression of UFL1. Furthermore, we found that UFL1 depletion caused a significant increase in apoptosis (increased the expression of BAX/BCL-2 and the activity of caspase-3). Conversely, the overexpression of UFL1 relieved the LPS-induced apoptosis. In order to assess whether the inhibition of bGCs apoptosis involved in the nuclear factor-κB (NF-κB) signaling pathway resulted from UFL1, we detected the expression of NF-κB p-p65. LPS treatment resulted in a significant upregulation in the protein concentration of NF-κB p-p65, and knockdown of UFL1 further increased the phosphorylation of NF-κB p65, while UFL1 overexpression significantly inhibited the expression of NF-κB p-p65. Collectively, UFL1 could suppress LPS-induced apoptosis in cow ovarian granulosa cells, likely via the NF-κB pathway. These results identify a novel role of UFL1 in the modulation of bGC apoptosis, which may be a potential signaling target to improve the reproductive health of dairy cows.

Cyclosporine A Inhibits tPA mRNA Transcription in A431 Cell Line

1996 ◽  
Vol 9 (2) ◽  
pp. 137-140 ◽  
Author(s):  
P. Teofoli ◽  
A. Mancini ◽  
T. Lotti
Keyword(s):  
Cell Line ◽  
Cyclosporine A ◽  
A431 Cell ◽  
Mrna Transcription ◽  
A431 Cell Line

Apoptotic signalling cascade in photosensitized human epidermal carcinoma A431 cells: involvement of singlet oxygen, c-Jun N-terminal kinase, caspase-3 and p21-activated kinase 2

2000 ◽  
Vol 351 (1) ◽  
pp. 221-232 ◽  
Author(s):  
Wen-Hsiung CHAN ◽  
Jau-Song YU ◽  
Shiaw-Der YANG
Keyword(s):  
Singlet Oxygen ◽  
Caspase 3 ◽  
Early Stage ◽  
A431 Cells ◽  
Caspase Family ◽  
P21 Activated Kinase ◽  
Induced Apoptosis ◽  
Jnk Activation ◽  
Epidermal Carcinoma ◽  
Signalling Cascade

Photodynamic treatment (PDT) elicits diverse cellular responses and can also cause apoptosis. In the present study the cascade of signalling events involved in PDT-induced apoptosis was investigated using Rose Bengal (RB) as the photosensitizer, and human epidermal carcinoma A431 cells as the cell model. We show that a 36-kDa kinase detected by an in-gel kinase assay is markedly activated during PDT-triggered apoptosis. Immunoblot analysis revealed that this 36-kDa kinase represents the C-terminal catalytic fragment of p21-activated kinase (PAK)2. Generation of this active fragment of PAK2 is mediated by the caspase family of proteases, which are activated by PDT. The specific caspase inhibitors (acetyl-Asp-Glu-Val-Asp-aldehyde and acetyl-Tyr-Val-Ala-Asp-chloromethylketone) block the PDT-induced caspase-3 activation and subsequent PAK2 cleavage/activation, indicating a major role for the caspase family proteases in PDT-induced apoptosis. Both PDT-induced caspase-3 activation and PAK2 cleavage/activation can be inhibited by the singlet oxygen scavengers, L-histidine and α-tocopherol, but not the hydroxyl radical scavenger, mannitol, demonstrating that singlet oxygen is an immediate early-apoptotic signal generated by PDT. In addition, PDT can induce a two-stage activation of the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) in A431 cells; the early-stage JNK activation is singlet oxygen-dependent, whereas the late-stage JNK activation is mediated by the singlet oxygen-triggered caspase activation. Experiments using anti-sense oligonucleotides against JNK1 and PAK2 further show that during PDT-induced apoptosis the early-stage JNK activation is required for caspase activation, and that the late-stage JNK activation is regulated by the caspase-mediated cleavage/activation of PAK2. Collectively, a model for the PDT-triggered apoptotic signalling cascade with RB is proposed, which involves singlet oxygen, JNK, caspase-3 and PAK2, sequentially.

scholarly journals An Anti-apoptotic Role of NF-κB in TNFα-induced Apoptosis in an Ameloblastoma Cell Line

2008 ◽  
Vol 5 (2) ◽  
pp. 96-103 ◽  
Author(s):  
Laifa Hendarmin ◽  
Shintaro Kawano ◽  
Daigo Yoshiga ◽  
Ferry Sandra ◽  
Takeshi Mitsuyasu ◽  
...  
Keyword(s):  
Cell Line ◽  
Induced Apoptosis

Role of Individual Amino Acids in the Action of Caspase Inhibitors as Proapoptotic Peptides for Human Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1998-1998
Author(s):  
Rebecca J. Asch ◽  
Nisha Shah ◽  
Tucker W. LeBien
Keyword(s):  
Cell Line ◽  
Stromal Cell ◽  
Parent Compound ◽  
Leukemic Cells ◽  
Caspase 9 ◽  
Caspase Inhibitors ◽  
B Lineage ◽  
Human Leukemic Cells ◽  
Induced Apoptosis

Abstract Three to five amino acid caspase inhibitors have been extensively used to identify the role of specific caspases in apoptotic pathways triggered by a wide range of cellular insults. Unexpectedly, we have recently demonstrated that the irreversible caspase-9 inhibitor (C9i) Z-LEHD-FMK can promote apoptosis in selected stressed and non-stressed human leukemic cells, and that inhibition of caspase-9 protein expression does not render cells more resistant to stress-induced apoptosis (Shah et al., Blood, in press 11/15/04). The goal of the current study was to analyze the role of caspase-9 in C9i-induced apoptosis, and the role of specific amino acids in the proapoptotic activity of C9i. We first determined whether cells made deficient in caspase-9 were still sensitive to the proapoptotic activity of C9i. Electroporation of the BLIN-4L stromal cell-dependent B-lineage ALL cell line and the RAMOS Burkitt lymphoma cell line with siRNA specific for caspase-9 led to >95% reduction of caspase-9 protein. Yet, both cells still exhibited a dose-dependent apoptotic response to C9i indistinguishable from cells electroporated with control siRNA. Since proapoptotic activity was not a property of inhibitors of caspases-2, 3, 6 and 8 (Shah et al.), we further examined the minimal structural requirements for the proapoptotic activity of C9i. The P1 aspartic acid and P3 glutamic acid are highly conserved in other caspase inhibitors that do not exhibit proapoptotic activity, so we initially focused on the P2 and P4 positions. The parent compound Z-LEHD-FMK was modified to yield Z-LEAD-FMK and Z-AEHD-FMK (synthesized by MP Biomedicals, Livermore, CA). Z-WEHD-FMK (commercially available as caspase-1 inhibitor) and Z-LEED-FMK (commercially available as caspase-13 inhibitor) were also studied. We tested several cell lines previously shown to be sensitive to C9i. As expected (Shah et al.), the BLIN-2, BLIN-3 and BLIN-4L adherent cell-dependent B-lineage ALL, the BLIN-1 pre-B ALL and the RAMOS Burkitt B cell lymphoma were sensitive to C9i as measured by TMRE and Annexin V staining. Strikingly, Z-LEAD-FMK and Z-LEED-FMK induced no apoptosis in the C9i sensitive targets. In contrast, Z-AEHD-FMK was weakly proapoptotic (at the maximum concentration of 100 μM) whereas Z-WEHD-FMK exhibited slightly greater proapoptotic activity than the parent compound Z-LEHD-FMK. Furthermore, Z-WEHD-FMK exhibited an overall pattern of proapoptotic activity against multiple sensitive and insensitive leukemic cell targets that was indistinguishable from Z-LEHD-FMK. Thus, the leucine at position P4 is expendable whereas the histidine at P2 is essential for proapoptotic activity of Z-LEHD-FMK. This pattern of apoptotic sensitivity to Z-LEHD-FMK and Z-WEHD-FMK extended to CD19+ B-lineage cells derived from cord blood HSC plated on the murine MS-5 stromal cell line. As a more stringent test of proapoptotic activity, the peptides were tested by limiting dilution analysis against RAMOS and K-562. Fifty μM Z-LEHD-FMK or 50 μM Z-WEHD-FMK exerted 2.5–3.0 log killing of RAMOS but had no effect on K-562. We conclude that selected peptides previously synthesized and widely used as caspase inhibitors harbor potent proapoptotic activity against human leukemic cells, which is unexpectedly distinct from their capacity to inhibit activated caspases.

An Alternatively Spliced Survivin Variant Is Positively Regulated by p53 and Sensitizes Leukemia Cells to Chemotherapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3497-3497
Author(s):  
Ningxi Zhu ◽  
Lubing Gu ◽  
Harry W. Findley ◽  
Fengzhi Li ◽  
Muxiang Zhou
Keyword(s):  
Cell Line ◽  
Lymphocytic Leukemia ◽  
Leukemia Cells ◽  
Temperature Sensitive ◽  
Permissive Temperature ◽  
Doxorubicin Treatment ◽  
Cryptic Exon ◽  
Apoptosis Protein ◽  
Induced Apoptosis

Abstract Survivin is a unique member of the inhibitor of apoptosis protein (IAP) family, and its expression is regulated by p53. Recent identification of several functionally divergent survivin variants augments the complexity of survivin action as well as its regulation. Here we report that survivin-2B (retaining a part of intron 2 as a cryptic exon) is positively regulated by p53, and its overexpression plays a role in sensitizing leukemia cells to chemotherapeutic drug doxorubicin. Doxorubicin treatment activated p53, downregulated survivin and survivin-DEx3 but upregulated survivin-2B in EU-3, an acute lymphocytic leukemia (ALL) cell line with wild type (wt)-p53 phenotype. In contrast, doxorubicin treatment failed to induce these alterations in EU-6 cells, a mutant-p53 ALL cell line. To specify the role of wt-p53 in regulating survivin and its variants, a temperature-sensitive p53 mutant plasmid p53–143 was transfected into EU-4, a p53-null ALL cell line, to establish a subline EU-4/p53–143. When EU-4/p53–143 cell culture was shifted from 37.5°C to the wt-p53-permissive temperature (32.5°C), the expression of survivin and survivin-DEx3 was decreased whereas survivin-2B expression was increased, confirming the distinct regulatory effect of p53 on survivin and its variants. To clarify the role of survivin-2B in the process of apoptosis, survivin-2B cDNA was cloned into pcDNA3HA vector and transfected into EU-4 cells. Enforced expression of survivin-2B in EU-4 cells inhibited cell growth and sensitized these cells to doxorubicin-induced apoptosis. These results suggest that survivin-2B variant is a pro-apoptotic factor and its expression is upregulated by p53.

Multiple Myeloma: Interleukin-15 Antagonizes Bone Morphogenetic Protein-Induced Apoptosis and Growth Inhibition.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3444-3444
Author(s):  
Magne Rekvig ◽  
Anne-Tove Brenne ◽  
Torstein Baade Ro ◽  
Anders Waage ◽  
Magne Borset ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Growth Inhibition ◽  
Cell Line ◽  
Caspase 3 ◽  
Myeloma Cell ◽  
Stimulus Figure ◽  
Myeloma Cell Line ◽  
Myeloma Cells ◽  
Induced Apoptosis

Abstract Multiple myeloma has two distinct features: Expansion of malignant plasma cells within the bone marrow accompanied by skeletal destruction. Bone morphogenetic proteins (BMPs) have been shown to induce apoptosis and inhibit growth in myeloma cells. BMPs are members of the TGF-β superfamily of proteins capable of inducing bone formation, and regulate proliferation, differentiation and apoptosis. We have investigated myeloma cell apoptosis and proliferation with BMP-4 and −6 in concert with the myeloma cell growth factors interleukin (IL)-2, IL-6, IL-10, IL-15, IL-21, tumor necrosis factor (TNF)-α and insulin-like growth factor (IGF)-1. Eight samples of highly purified myeloma cells from patients and a human myeloma cell line, IH-1 (Brenne AT et al. Blood. 2002 May 15;99(10):3756–62.), were used in this study. Cytokine concentrations used in the referred experiments were for BMP-4 20ng/ml, BMP-6 250ng/ml, IL-15 20ng/ml and IL-6 0,1ng/ml, respectively. Growth inhibition was measured in a proliferation assay by methyl-[3H]-thymidine incorporation and apoptosis by annexin V- FITC-binding/PI-uptake on flow cytometry. IL-15 antagonized growth inhibition (Figure A) and prevented apoptosis induced by BMP-4 (Figure B) and BMP-6 in the myeloma cell line IH-1. IL-15 also antagonized the growth inhibition induced by BMP-4 and/or BMP-6 in three out of eight patient samples. Neither IL-6, nor any of the other investigated cytokines were able to rescue the myeloma cells from growth inhibition and apoptosis induced by BMP-4 and -6. Among the investigated cytokines, we found that IL-15 has a unique capability to antagonize BMP- induced apoptosis and growth inhibition in myeloma cells. We examined cleavage of the proapoptotic protein caspase-3 and found that BMP-4 activated caspase-3 in the IH-1 cell line. This activation of caspase-3 was blocked by IL-15 but not by IL-6. We have demonstrated a possible mechanism for myeloma cells to escape apoptosis and growth-inhibition within the bone marrow. Intramedullar levels of IL-15 and BMPs may play a role in the pathogenesis of multiple myeloma. Figure A. Proliferation in response to BMP-4 stimulus Figure A. Proliferation in response to BMP-4 stimulus Figure B. Apoptosis in response to BMP-4 stimulus Figure B. Apoptosis in response to BMP-4 stimulus

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