scholarly journals Heat shock and tumor necrosis factor-α induce apoptosis in bovine preimplantation embryos through a caspase-9-dependent mechanism

Reproduction ◽  
2007 ◽  
Vol 133 (6) ◽  
pp. 1129-1137 ◽  
Author(s):  
Bárbara Loureiro ◽  
Amber Mary Brad ◽  
Peter James Hansen
Keyword(s):  
Heat Shock ◽  
Tumor Necrosis ◽  
Preimplantation Embryos ◽  
Caspase 8 ◽  
Mitochondrial Depolarization ◽  
Caspase 9 ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor ◽  
Dependent Mechanism

Heat shock and tumor necrosis factor-α (TNF-α) induce apoptosis through different mechanisms, with heat shock acting to cause mitochondrial depolarization and caspase-9 activation, while TNF-α acts through a receptor-mediated process to activate caspase-8. In some cells, however, TNF-α can also cause mitochondrial depolarization and caspase-9 activation. In the present study, we tested the hypothesis that heat shock at 41 °C and TNF-α induce apoptosis in bovine preimplantation embryos through a caspase-9-dependent mechanism. Treatment of embryos with either heat shock (41 °C) or TNF-α increased the proportion of blastomeres that were TUNEL positive and the proportion of embryos exhibiting elevated caspase-9 activity. Furthermore, the caspase-9 inhibitor, z-LEHD-fmk, blocked the increase in TUNEL-positive nuclei caused by both heat shock and TNF-α. For embryos at day 6 after insemination, for example, the percent of blastomeres positive for TUNEL was 3.6% for control embryos, 11.1% for embryos cultured at 41 °C, and 15.1% for embryos cultured with 10 ng/ml TNF-α. In the presence of z-LEHD-fmk, the percent of cells positive for TUNEL was 3.7% for control embryos, 6.1% for embryos cultured at 41 °C, and 8% for embryos cultured with 10 ng/ml TNF-α. Although TNF-α did not cause a measurable increase in caspase-8 activity, there was a tendency (P= 0.07) for treatment of embryos with z-IETD-fmk, an inhibitor of caspase-8, to partly reduce the magnitude of the increase in TUNEL-positive cells caused by TNF-α. The percent of cells that were TUNEL positive was increased by TNF-α from 9.7 to 19.7% in the absence of inhibitor and from 13.0 to 15.6% in the presence of z-IETD-fmk. Results indicate that induction of apoptosis by both heat shock and TNF-α involve activation of caspase-9-dependent pathways. It is likely that TNF-α also activates apoptotic pathways involving caspase-8 but that the degree of activation is small and caspase-9-dependent pathways are required for full activation of apoptosis.

133 ROLE OF CASPASE-9 AND STAGE OF DEVELOPMENT IN INDUCTION OF APOPTOSIS BY HEAT SHOCK AND TUMOR NECROSIS FACTOR-α IN BOVINE PRE-IMPLANTATION EMBRYOS

2006 ◽  
Vol 18 (2) ◽  
pp. 175
Author(s):  
B. Loureiro ◽  
A. M. Brad ◽  
P. J. Hansen
Keyword(s):  
Heat Shock ◽  
Tumor Necrosis ◽  
Cell Number ◽  
Caspase 9 ◽  
Stage Of Development ◽  
Tnf Α ◽  
Induction Of Apoptosis ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Necrosis Factor

Heat shock and tumor necrosis factor-α (TNF-α) can increase apoptosis in bovine embryos in a developmental-dependent manner. It was hypothesized that addition of the caspase-9 inhibitor, z-LEHD-fmk, would block induction of apoptosis caused by heat shock of 41°C and TNF-α. Furthermore, it was hypothesized that the magnitude of induced apoptosis would increase with stage of development. Embryos were collected on day 4, 5, and 6 after in vitro insemination and were cultured for 24 h in the presence of either 100 μm z-LEHD-fmk reconstituted in 0.5% (v/v) dimethyl sulfoxide or vehicle dimethyl sulfoxide at either (1) 38.5°C for 24 h (control), (2) 41°C for 15 h followed by 38.5°C for 9 h, or (3) 38.5°C for 24 h with 10 ng/mL murine TNF-α. Embryos were then fixed, and the proportion of blastomeres undergoing apoptosis was determined using TUNEL labeling. Heat shock did not increase the percentage of blastomeres that were TUNEL-positive (% apoptosis) at day 4 (n = 100 embryos total). In contrast, heat shock increased % apoptosis at day 5 and day 6 (P < 0.04) and this effect was blocked by z-LEHD-fmk (temperature × inhibitor, P < 0.04). At day 5, % apoptosis in the absence and presence of z-LEHD-fmk was 3.8 ± 1.9% and 3.7 ± 1.7% at 38.5°C vs. 8.9 ± 1.5% and 4.1 ± 1.7% at 41°C (n = 75 embryos total). At day 6, % apoptosis in the absence and presence of z-LEHD-fmk was 3.6 ± 1.1% and 3.7 ± 1.2% at 38.5°C vs. 11.1 ± 1.1% and 6.1 ± 1.2% at 41°C (n = 168 embryos total). Mean cell number at the end of culture ranged from 21 to 26 cells at day 4, 43 to 73 cells at day 5, and 101 to 114 cells at day 6. Treatment with TNF-α also increased apoptosis at all days (P < 0.01), and z-LEHD-fmk blocked this effect (TNF × inhibitor, P = 0.05; n = 361 embryos total). Across days, % apoptosis was 3.6 ± 1.4% (control), 3.3 ± 1.3% (inhibitor), 11.1 ± 1.3% (TNF-α), and 6.0 ± 1.4% (TNF-α + inhibitor). Mean cell number at the end of culture ranged from 21 to 27 cells at day 4, 59 to 74 cells at day 5, and 105 to 115 cells at day 6. In conclusion, activation of caspase-9 dependent pathways is involved in the induction of apoptosis by heat shock and TNF-α. Moreover, the magnitude of induced apoptosis increases as embryos advance in development. This work was supported by USDA Grant No. 2004–34135–14715 and BARD Grant No. US–3551–04.

scholarly journals Tumor Necrosis Factor-α, Caspase-9 and Heat Shock Protein 70 Expressions with Leukemia Inhibitory Factor in Hydrosalpinx

2020 ◽  
Author(s):  
Hanom Husni Syam ◽  
Tono Djuwantono ◽  
Jusuf S. Effendi ◽  
Ponpon S. Idjradinata ◽  
Tita H. Madjid ◽  
...  
Keyword(s):  
Heat Shock ◽  
Leukemia Inhibitory Factor ◽  
Heat Shock Protein 70 ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Endometrial Receptivity ◽  
Caspase 9 ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Abstract Background The leakage of hydrosalpinx fluid from the tube into the uterine cavity is likely to interfere with normal implantation. Hydrosalpinx fluids contain tumor necrosis factor-α (TNF-α), which induces caspase-9 signal transduction, leading to apoptosis. Endometrial cells inhibit apoptosis by synthesizing heat shock protein 70 (Hsp70). The TNF-α, caspase-9 and Hsp70 factors are closely related to apoptosis. In women with hydrosalpinx, the endometrial receptivity of embryonic implantation processes is low. Endometrial receptivity can be assessed by leukemia inhibitory factor (LIF). TNF-α, caspase-9 and Hsp70 expression plays an important role in endometrial receptivity disorders in women with hydrosalpinx.Materials and Methods These is an analytic observational, cross-sectional and categorical comparative study was conducted in 44 subjects with and without hydrosalpinx. The present study was performed in Dr. Hasan Sadikin Hospital, Grha Bunda-, Limijati-Maternity and Children Hospital (May-June 2017). Immunohistochemistry was performed with a cutoff based on the ROC. The Mann-Whitney analysis was performed on TNF-α, caspase-9, Hsp70 and LIF in both groups, whereas a correlation regression test was performed to observe the correlation among these protein.Results The present study used the histoscore as a tool to evaluate the expression of variable between study groups. The comparison of the histoscore for parameters between hydrosalpinx and non-hydrosalpinx subjects was TNF-α (12 vs 9; p<0,001), caspase-9 (12 vs 8,5; p<0,001), Hsp70 (6 vs 8; p<0,001), and LIF (9 vs 12; p<0,05), respectively.Conclusion The results showed a significant difference in TNF-α, caspase-9, Hsp70 and LIF (p <0.05) between hydrosalpinx and non-hydrosalpinx patients. Caspase-9 and Hsp70 are inter-connected and related to LIF as a marker in the endometrium receptivity by hydrosalpinx patients.

scholarly journals Contrasting Effects of IG20 and Its Splice Isoforms, MADD and DENN-SV, on Tumor Necrosis Factor α-induced Apoptosis and Activation of Caspase-8 and -3

2001 ◽  
Vol 276 (50) ◽  
pp. 47202-47211 ◽  
Author(s):  
Adeeb M. Al-Zoubi ◽  
Elena V. Efimova ◽  
Shashi Kaithamana ◽  
Osvaldo Martinez ◽  
Mohammed El-Azami El-Idrissi ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Single Gene ◽  
Caspase 8 ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Necrosis Factor

We identified a novel cDNA (IG20) that is homologous to cDNAs encoding a proteindifferentiallyexpressed innormal andneoplastic cells (DENN-SV) and human MADD (MAPK-activatingdeathdomain-containing protein). Furthermore, we show that the above variants most likely result from alternative splicing of a single gene. Functional analyses of these variants in permanently transfected HeLa cells revealed that IG20 and DENN-SV render them more susceptible or resistant to tumor necrosis factor α (TNF-α)-induced apoptosis, respectively. All variants tested could interact with TNF receptor 1 and activate ERK and nuclear factor κB. However, relative to control cells, only cells expressing IG20 showed enhanced TNF-α-induced activation of caspase-8 and -3, whereas cells expressing DENN-SV showed either reduced or no caspase activation. Transfection of these cells with a cDNA encoding CrmA maximally inhibited apoptosis in HeLa-IG20 cells. Our results show that IG20 can promote TNF-α-induced apoptosis and activation of caspase-8 and -3 and suggest that it may play a novel role in the regulation of the pleiotropic effects of TNF-α through alternative splicing.

scholarly journals Perbandingan Kadar Heat Shock Protein 90 dan Tumor Necrosis Factor-α Antara Kehamilan Preterm Dengan Ketuban Pecah Dini dan Tanpa Ketuban Pecah Dini

2018 ◽  
Vol 7 ◽  
pp. 54
Author(s):  
Riri Karnain ◽  
Yusrawati Yusrawati ◽  
Erkadius Erkadius
Keyword(s):  
Heat Shock ◽  
Tumor Necrosis Factor ◽  
Heat Shock Protein ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Heat Shock Protein 90 ◽  
Tnf Α ◽  
Factor Α ◽  
Hsp 90 ◽  
Necrosis Factor

Ketuban pecah dini (KPD) berkaitan dengan peningkatan kadar Heat Shock Protein 90 (HSP 90) dan Tumor Necrosis Factor-α (TNF-α) yang muncul akibat stres oksidatif. Tujuan penelitian ini adalah membandingkan kadar HSP 90 dan TNF-α antara kehamilan preterm dengan KPD dan tanpa KPD. Penelitian ini menggunakan rancangan comparative study yang dilaksanakan di RSUD dr. Rasidin, RS Tk.III Reksodiwiryo, RS Bhayangkara, Puskesmas Lubuk Buaya dan Laboratorium Biomedik Fakultas Kedokteran Universitas Andalas dari bulan Oktober 2017 sampai Juli 2018. Jumlah sampel sebanyak 24 ibu hamil preterm dengan KPD dan 24 ibu hamil preterm tanpa KPD dengan menggunakan teknik consecutive sampling. Pemeriksaan HSP 90 dan TNF-α menggunakan metode ELISA. Uji normalitas data dengan uji Shapiro-Wilk. Analisis data komparatif menggunakan uji Mann-Whitney. Median kadar HSP 90 yaitu 11,21 ng/mL pada kehamilan preterm dengan KPD dan 9,15 ng/mL pada kehamilan preterm tanpa KPD dengan nilai p < 0,05. Median kadar TNF-α yaitu 0,21 ng/mL pada kehamilan preterm dengan KPD dan 0,17 ng/mL pada kehamilan preterm tanpa KPD dengan nilai p < 0,05. Kadar HSP 90 dan TNF-α pada kehamilan preterm dengan KPD lebih tinggi secara bermakna dibandingkan pada kehamilan preterm tanpa KPD.

Modulation of HSP25 and TNF-α during the early stages of functional overload of a rat slow and fast muscle

2007 ◽  
Vol 102 (6) ◽  
pp. 2307-2314 ◽  
Author(s):  
Kimberly A. Huey ◽  
Gary E. McCall ◽  
Hui Zhong ◽  
Roland R. Roy
Keyword(s):  
Heat Shock ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Soluble Fraction ◽  
Insoluble Fraction ◽  
Mrna Levels ◽  
Tnf Α ◽  
Muscle Loading ◽  
Factor Α ◽  
Necrosis Factor

Early events in response to abrupt increases in activation and loading with muscle functional overload (FO) are associated with increased damage and inflammation. Heat shock protein 25 (HSP25) may protect against these stressors, and its expression can be regulated by muscle loading and activation. The purpose of this study was to investigate the responses of HSP25, phosphorylated HSP25 (pHSP25), and tumor necrosis factor-α (TNF-α) during FO of the slow soleus and fast plantaris. We compared the HSP25 mRNA, HSP25 protein, pHSP25, and TNF-α responses in the soleus and plantaris after 0.5, 1, 2, 3, and 7 days of FO. HSP25 and pHSP25 were quantified in soluble and insoluble fractions. HSP25 mRNA increased immediately in both muscles and decreased with continued FO. However, HSP25 mRNA levels were consistently higher in the muscles of FO than control rats. In the soluble fraction, HSP25 increased in the plantaris after 2–7 days of FO with the greatest response at 3 and 7 days. The pHSP25 response to FO was greater in the plantaris than soleus at all points in the soluble fraction and at 0.5 days in the insoluble fraction. TNF-α levels in the plantaris, but not soleus, were higher than control at 0.5–2 days of FO. This may have contributed to the greater FO response in pHSP25 in the plantaris than soleus as TNF-α increased pHSP25 in C2C12 myotubes. These results suggest that the initial responses of pHSP25 and TNF-α to mechanical stress and inflammation associated with FO are greater in a fast than slow extensor muscle.

#50 Gestational exposure of tumor necrosis factor-α (TNF-α) inhibitor drugs

2019 ◽  
Vol 88 ◽  
pp. 149-150 ◽  
Author(s):  
Erkoseoglu Ilknur ◽  
Kadioglu Mine ◽  
Cavusoglu Irem ◽  
Sisman Mulkiye ◽  
Aran Turhan ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Gestational Exposure ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Tumor Necrosis Factor-α Production-Enhancing Properties of Novel Adamantylalkylthio Derivatives of Some Heterocyclic Compounds

2005 ◽  
Vol 60 (4) ◽  
pp. 471-475 ◽  
Author(s):  
Barbara Orzeszko ◽  
Tomasz Świtaj ◽  
Anna B. Jakubowska-Mućka ◽  
Witold Lasek ◽  
Andrzej Orzeszko ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Heterocyclic Compounds ◽  
Tumor Necrosis ◽  
The Novel ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Factor Α ◽  
Derivatives Of ◽  
Necrosis Factor

Certain adamantylated heterocycles were previously shown to enhance the secretion of tumor necrosis factor alpha (TNF-α) by murine melanoma cells that have been transduced with the gene for human TNF-α and constitutively expressed this cytokine. The stimulatory potency of those compounds depended, among other factors, on the structure of the linker between the adamantyl residue and the heterocyclic core. In the present study, a series of (1-adamantyl)alkylsulfanyl derivatives of heterocyclic compounds was prepared by alkylation of the corresponding thioheterocyles. Of the novel adamantylalkylthio compounds tested in the aforementioned cell line, 2-(2-adamantan-1-ylethylsulfanyl)- 4-methyl-pyrimidine was found to be the most active

scholarly journals Tumor necrosis factor α Inhibition for Alzheimer’s Disease

2017 ◽  
Vol 9 ◽  
pp. 117957351770927 ◽  
Author(s):  
Rudy Chang ◽  
Kei-Lwun Yee ◽  
Rachita K Sumbria
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Short Review ◽  
Tnf Α ◽  
Factor Α ◽  
Ad Therapy ◽  
Necrosis Factor

Tumor necrosis factor α (TNF-α) plays a central role in the pathophysiology of Alzheimer’s disease (AD). Food and Drug Administration–approved biologic TNF-α inhibitors are thus a potential treatment for AD, but they do not cross the blood-brain barrier. In this short review, we discuss the involvement of TNF-α in AD, challenges associated with the development of existing biologic TNF-α inhibitors for AD, and potential therapeutic strategies for targeting TNF-α for AD therapy.

Tumor necrosis factor-α-associated lysosomal permeabilization is cathepsin B dependent

2002 ◽  
Vol 283 (4) ◽  
pp. G947-G956 ◽  
Author(s):  
Nathan W. Werneburg ◽  
M. Eugenia Guicciardi ◽  
Steven F. Bronk ◽  
Gregory J. Gores
Keyword(s):  
Tumor Necrosis Factor ◽  
Cathepsin B ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Fluorescent Protein ◽  
Tnf Α ◽  
Calcein Release ◽  
Green Fluorescent ◽  
Factor Α ◽  
Necrosis Factor

Cathepsin B (Cat B) is released from lysososomes during tumor necrosis factor-α (TNF-α) cytotoxic signaling in hepatocytes and contributes to cell death. Sphingosine has recently been implicated in lysosomal permeabilization and is increased in the liver by TNF-α. Thus the aims of this study were to examine the mechanisms involved in TNF-α-associated lysosomal permeabilization, especially the role of sphingosine. Confocal microscopy demonstrated Cat B-green fluorescent protein and LysoTracker Red were both released from lysosomes after treatment of McNtcp.24 cells with TNF-α/actinomycin D, a finding compatible with lysosomal destabilization. In contrast, endosomes labeled with Texas Red dextran remained intact, suggesting lysosomes were specifically targeted for permeabilization. LysoTracker Red was released from lysosomes in hepatocytes treated with TNF-α or sphingosine in Cat B(+/+) but not Cat B(−/−) hepatocytes, as assessed by a fluorescence-based assay. With the use of a calcein release assay in isolated lysosomes, sphingosine permeabilized liver lysosomes isolated from Cat B(+/+) but not Cat B(−/−) liver. C6ceramide did not permeabilize lysosomes. In conclusion, these data implicate a sphingosine-Cat B interaction inducing lysosomal destabilization during TNF-α cytotoxic signaling.

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