scholarly journals 222THE ROLE OF TUMOR NECROSIS FACTOR-RELATED APOPTOSIS INDUCING LIGAND DURING FOLLICULAR ATRESIA IN PIG OVARIES

2004 ◽  
Vol 16 (2) ◽  
pp. 232
Author(s):  
N. Inoue ◽  
N. Manabe ◽  
M. Nakayama ◽  
T. Matsui ◽  
A. Maeda ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Granulosa Cells ◽  
Tumor Necrosis ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Follicular Atresia ◽  
Rt Pcr ◽  
Antral Follicles ◽  
Necrosis Factor

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce cell death by binding to its receptors (DR4 and DR5). However, binding to DcR1 or DcR2 cannot induce apoptosis. DcRs compete with DRs. TRAIL has been reported to induce apoptosis in various tumor cells but not in normal cells. However, a recent study revealed that TRAIL induces apoptosis in normal hepatocytes of human but not in those of rat, mouse, or rhesus monkey, indicating that there are species-specific differences in TRAIL and receptor systems. In the present study, we demonstrated Immunohistochemical, Western immunoblotting, and reverse transcription-polymerase chain reaction analyses (RT-PCR) of TRAIL and DR4 in granulosa cells during follicular atresia in pig ovaries. For immunohistochemistry, pig ovaries obtained at a local slaughterhouse were fixed with 20% buffered formalin. For Western blotting and RT-PCR analysis, individual preovulatory antral follicles were dissected from the ovaries. Based on morphological and endocrinological criteria, the antral follicles were divided into three categories as follows: healthy, early stage of atresia, progressed stage of atresia. Significant increases were demonstrated in TRAIL protein and mRNA levels during atresia, but not in DR4 protein. Moreover in an in vitro apoptosis-inducing assay using cultured granulosa cells prepared from healthy follicles, we showed that more than 200ng/mL TRAIL could activate caspase-3 and induce apoptotic cell death in a dose-and time-dependent manner, but less than 100ng/mL of TRAIL could not induce apoptosis. When DcR1 was removed from the cell membrane of granulosa cells, a lower dose of TRAIL could induce apoptosis. The present findings suggested that the TRAIL can induce granulosa cell apoptosis, and that DcR1 blocks TRAIL-induced apoptosis in granulosa cells of healthy follicles in porcine ovaries.

scholarly journals Tumor necrosis factor-related apoptosis inducing ligand expression and activity in hen granulosa cells

Reproduction ◽  
2007 ◽  
Vol 133 (3) ◽  
pp. 609-616 ◽  
Author(s):  
A L Johnson ◽  
Christine Ratajczak ◽  
Morgan J Haugen ◽  
Han-Ken Liu ◽  
Dori C Woods
Keyword(s):  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Cell Viability ◽  
Granulosa Cells ◽  
Tumor Necrosis ◽  
Caspase 3 ◽  
Cell Death Pathway ◽  
Wide Range ◽  
Trail Signaling ◽  
Necrosis Factor

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) represents one of several cytokine members of the tumor necrosis factor superfamily reported to initiate apoptosis in a wide range of transformed, but not most normal, cell types. The present studies were conducted to evaluate the potential for TRAIL to promote apoptotic cell death in differentiated granulosa cells collected from hen preovulatory follicles. While mRNA encoding critical components (including TRAIL) required for a functional extrinsic cell death pathway are expressed in granulosa cells, TRAIL treatment by itself fails to induce either caspase-3 activity or a decrease in cell viability. On the other hand, preculture of cells with the conventional chemotherapeutic, cisplatin, or the 20S proteosome inhibitor, Z-LLF-CHO, sensitizes granulosa cells to TRAIL as evidenced by enhanced caspase-3 activity after 4 h of culture and loss of cell viability after 24 h when compared with either cisplatin or Z-LLF-CHO treatment alone. Moreover, the sensitizing effect of Z-LLF-CHO on TRAIL-induced loss of cell viability is prevented by the selective caspase-8 inhibitor, Z-IETD-FMK. Interestingly, TRAIL mRNA expression is elevated both in prehierarchal follicles undergoing spontaneous atresia and in prehierarchal follicles induced to undergo atresia for 6 h in vitro. In summary, the data demonstrate the presence of a functional TRAIL signaling pathway in hen granulosa cells, and are consistent with the possibility that TRAIL signaling may directly or indirectly participate in the process of follicle atresia in vivo.

scholarly journals Tumor Necrosis Factor Receptor-associated Protein 1 (TRAP1) Mutation and TRAP1 Inhibitor Gamitrinib-triphenylphosphonium (G-TPP) Induce a Forkhead Box O (FOXO)-dependent Cell Protective Signal from Mitochondria

2015 ◽  
Vol 291 (4) ◽  
pp. 1841-1853 ◽  
Author(s):  
Hyunjin Kim ◽  
Jinsung Yang ◽  
Min Ju Kim ◽  
Sekyu Choi ◽  
Ju-Ryung Chung ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Mitochondrial Dysfunction ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Dependent Manner ◽  
Neuron Loss ◽  
Receptor Associated Protein ◽  
Necrosis Factor

TRAP1 (tumor necrosis factor receptor-associated protein 1), a mitochondrial Hsp90 family chaperone, has been identified as a critical regulator of cell survival and bioenergetics in tumor cells. To discover novel signaling networks regulated by TRAP1, we generated Drosophila TRAP1 mutants. The mutants successfully developed into adults and produced fertile progeny, showing that TRAP1 is dispensable in development and reproduction. Surprisingly, mutation or knockdown of TRAP1 markedly enhanced Drosophila survival under oxidative stress. Moreover, TRAP1 mutation ameliorated mitochondrial dysfunction and dopaminergic (DA) neuron loss induced by deletion of a familial Parkinson disease gene PINK1 (Pten-induced kinase 1) in Drosophila. Gamitrinib-triphenylphosphonium, a mitochondria-targeted Hsp90 inhibitor that increases cell death in HeLa and MCF7 cells, consistently inhibited cell death induced by oxidative stress and mitochondrial dysfunction induced by PINK1 mutation in mouse embryonic fibroblast cells and DA cell models such as SH-SY5Y and SN4741 cells. Additionally, gamitrinib-triphenylphosphonium also suppressed the defective locomotive activity and DA neuron loss in Drosophila PINK1 null mutants. In further genetic analyses, we showed enhanced expression of Thor, a downstream target gene of transcription factor FOXO, in TRAP1 mutants. Furthermore, deletion of FOXO almost nullified the protective roles of TRAP1 mutation against oxidative stress and PINK1 mutation. These results strongly suggest that inhibition of the mitochondrial chaperone TRAP1 generates a retrograde cell protective signal from mitochondria to the nucleus in a FOXO-dependent manner.

scholarly journals Role of arachidonic acid metabolism in transcriptional induction of tumor necrosis factor gene expression by phorbol ester.

1989 ◽  
Vol 9 (1) ◽  
pp. 252-258 ◽  
Author(s):  
J Horiguchi ◽  
D Spriggs ◽  
K Imamura ◽  
R Stone ◽  
R Luebbers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Arachidonic Acid ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Leukotriene B4 ◽  
Mrna Levels ◽  
Arachidonic Acid Release ◽  
Acid Release ◽  
Tnf Gene ◽  
Necrosis Factor

The treatment of human HL-60 promyelocytic leukemia cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with induction of tumor necrosis factor (TNF) transcript. The study reported here has examined TPA-induced signaling mechanisms responsible for the regulation of TNF gene expression in these cells. Run-on assays demonstrated that TPA increases TNF mRNA levels by transcriptional activation of this gene. The induction of TNF transcripts by TPA was inhibited by the isoquinolinesulfonamide derivative H7 but not by HA1004, suggesting that this effect of TPA is mediated by activation of protein kinase C. TPA treatment also resulted in increased arachidonic acid release. Moreover, inhibitors of phospholipase A2 blocked both the increase in arachidonic acid release and the induction of TNF transcripts. These findings suggest that TPA induces TNF gene expression through the formation of arachidonic acid metabolites. Although indomethacin had no detectable effect on this induction of TNF transcripts, ketoconazole, an inhibitor of 5-lipoxygenase, blocked TPA-induced increases in TNF mRNA levels. Moreover, TNF mRNA levels were increased by the 5-lipoxygenase metabolite leukotriene B4. In contrast, the cyclooxygenase metabolite prostaglandin E2 inhibited the induction of TNF transcripts by TPA. Taken together, these results suggest that TPA induces TNF gene expression through the arachidonic acid cascade and that the level of TNF transcripts is regulated by metabolites of the pathway, leukotriene B4 and prostaglandin E2.

scholarly journals Tumor Necrosis Factor-α Increases ATP Content in Metabolically Inhibited L929 Cells Preceding Cell Death

1997 ◽  
Vol 272 (48) ◽  
pp. 30167-30177 ◽  
Author(s):  
José A. Sánchez-Alcázar ◽  
Jesús Ruı́z-Cabello ◽  
Inmaculada Hernández-Muñoz ◽  
Pilar Sánchez Pobre ◽  
Paz de la Torre ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Atp Content ◽  
L929 Cells ◽  
Factor Α ◽  
Necrosis Factor ◽  
Preceding Cell

scholarly journals T cell receptor-dependent cell death of T cell hybridomas mediated by the CD30 cytoplasmic domain in association with tumor necrosis factor receptor-associated factors.

1996 ◽  
Vol 183 (2) ◽  
pp. 669-674 ◽  
Author(s):  
S Y Lee ◽  
C G Park ◽  
Y Choi
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
T Cell Receptor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Cell Receptor ◽  
Cytoplasmic Domain ◽  
Activated T Cells ◽  
Necrosis Factor

CD30 is a member of the tumor necrosis factor superfamily and a surface marker for Hodgkin's disease. Normal activated T cells and several virally transformed T or B cell lines also show CD30 expression. The interaction of CD30 with its ligand induces cell death or proliferation, depending on the cell type. In this report we characterize the signals mediated by the intracellular domain of CD30 and show that, in combination with signal(s) transduced by the T cell receptor, the multimerization of CD30 cytoplasmic domain induces Fas(CD95)-independent cell death in T cell hybridomas. Deletion analysis shows that the COOH-terminal 66 amino acids of CD30 are required to induce cell death. Using the yeast two-hybrid system, we have identified that the same region of CD30 interacts with tumor necrosis factor receptor-associated factor (TRAF)1 and TRAF2. These results indicate that TRAF1 and/or TRAF2 play an important role in cell death in addition to their previously identified roles in cell proliferation.

scholarly journals Differentiation factor/leukemia inhibitory factor protection against lethal endotoxemia in mice: synergistic effect with interleukin 1 and tumor necrosis factor.

1992 ◽  
Vol 175 (4) ◽  
pp. 1139-1142 ◽  
Author(s):  
H R Alexander ◽  
G G Wong ◽  
G M Doherty ◽  
D J Venzon ◽  
D L Fraker ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Leukemia Inhibitory Factor ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Inhibitory Factor ◽  
Dependent Manner ◽  
Lps Challenge ◽  
Differentiation Factor ◽  
Dose Dependent ◽  
Necrosis Factor

Differentiation factor (D factor), also called leukemia inhibitory factor (LIF), is a glycoprotein that has been increasingly recognized to possess a wide range of physiological activities. We examined the possibility that the administration of D factor may confer beneficial effects and enhance host resistance against lethal endotoxemia. A single intravenous dose of recombinant human D factor completely protected C57/Bl6 mice from the lethal effect of Escherichia coli endotoxin (lipopolysaccharide [LPS]). The protective effects were dose dependent and observed when administered 2-24 h before LPS. Previous work has shown that interleukin 1 (IL-1) and tumor necrosis factor (TNF) also protect against a subsequent LPS challenge in a dose-dependent manner. When human D factor was combined with sub-protective doses of IL-1 beta or TNF-alpha, there was dramatic synergistic protection against a subsequent lethal LPS challenge.

scholarly journals Monocytes Treated with Human Immunodeficiency Virus Tat Kill Uninfected CD4+ Cells by a Tumor Necrosis Factor-Related Apoptosis-Induced Ligand-Mediated Mechanism

2003 ◽  
Vol 77 (12) ◽  
pp. 6700-6708 ◽  
Author(s):  
Yida Yang ◽  
Ilia Tikhonov ◽  
Tracy J. Ruckwardt ◽  
Mahmoud Djavani ◽  
Juan Carlos Zapata ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cell Surface Expression ◽  
Monocyte Subset ◽  
Hiv Tat ◽  
Immunodeficiency Virus ◽  
Necrosis Factor

ABSTRACT The human immunodeficiency virus (HIV) Tat protein has a critical role in viral transcription, but this study focuses on its additional role as an extracellular effector of lymphocyte cell death. It is well known that Tat induces tumor necrosis factor-related apoptosis-induced ligand (TRAIL) in peripheral blood mononuclear cells (PBMC), and we show that the majority of TRAIL is produced by the monocyte subset of PBMC. Human monocytes and U937 monoblastoid cells did not take up soluble HIV Tat-86, as T cells did, yet produced more TRAIL than did T cells. TRAIL secretion was induced by Tat and by a cysteine-rich peptide of Tat but not by sulfhydryl-modified Tat toxoid. Although there was only a slight increase in cell surface expression of TRAIL on monocytes, sufficient TRAIL was secreted to be toxic for T cells. The cytotoxicity of Tat-stimulated monocyte medium could be blocked by a TRAIL-neutralizing antibody. T cells treated with Tat did not secrete enough TRAIL to mediate cell death in our assay. Remarkably, uninfected T cells are more susceptible to TRAIL than are HIV-infected T cells. The production of TRAIL by Tat-stimulated monocytes provides a mechanism by which HIV infection can destroy uninfected bystander cells.

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