Dynamic Effect of Heat Shock Pretreatment on Apoptotic Responses to TNF-α in Liver Cells

2009 ◽  
Vol 131 (7) ◽  
Author(s):  
Sihong Wang ◽  
Pohun C. Chen ◽  
Francois Berthiaume ◽  
Mehmet Toner ◽  
Arul Jayaraman ◽  
...  
Keyword(s):  
Heat Shock ◽  
Dynamic Change ◽  
Dynamic Effect ◽  
Protective Mechanism ◽  
Clinical Approach ◽  
Target Tissue ◽  
Tnf Α ◽  
Tunel Reaction ◽  
Induced Apoptosis ◽  
Factor Α

The heat shock (HS) response is a protective mechanism for cells to protect themselves against subsequent lethal stress. HS upregulated heat shock protein (HSP) expression reduced apoptosis following tumor necrosis factor-α (TNF-α) stimulation. However, vector-mediated overexpression of HSP70 failed to provide similar protection but rather sensitized cells to TNF-α induced apoptosis. This may be due to the fact that the kinetics of vector-mediated HSP overexpression is totally different from that of HSP upregulation by HS. We hypothesized that the response depends on the timing of TNF-α challenge relative to HSP expression dynamics after HS. Therefore, we investigated the correlation between the dynamic change of HSP expression and the levels of apoptosis induced by TNF-α after HS. Hepatoma cells were subjected to mild heat shock at 42°C for 2 h followed by varied recovery times and then treated with TNF-α to induce apoptosis. The results from quantitative apoptosis assays using the TUNEL reaction reveal an optimal HS protection window centered around 5 h post-HS against TNF-α induced apoptosis. In addition, we found a window extending up to 2 h after HS where HS sensitized cells to TNF-α stress. Importantly, the correlation between apoptosis and HSP expression kinetics demonstrates that both high levels of HSPs and proper timing between HS and TNF-α stress were critical for optimal protection. Our study establishes a dynamic experimental model for further investigation of HS as a potential clinical approach to target tissue survival or death.

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 The protective mechanism of Ginkgolides and Ginkgo flavonoids on the TNF-α induced apoptosis of rat hippocampal neurons and its mechanisms in vitro

Heliyon ◽  
2015 ◽  
Vol 1 (1) ◽  
pp. e00020 ◽  
Author(s):  
Maojuan Guo ◽  
Yanrong Suo ◽  
Qing Gao ◽  
Huan Du ◽  
Wenyun Zeng ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Protective Mechanism ◽  
Tnf Α ◽  
Induced Apoptosis

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.

Differential protective effects of Bcl-xL and Bcl-2 on apoptotic liver injury in transgenic mice

1999 ◽  
Vol 277 (3) ◽  
pp. G702-G708 ◽  
Author(s):  
Alix de la Coste ◽  
Monique Fabre ◽  
Nathalie McDonell ◽  
Arlette Porteu ◽  
Helène Gilgenkrantz ◽  
...  
Keyword(s):  
Liver Injury ◽  
Transgenic Mice ◽  
Fas Ligand ◽  
Dependent Manner ◽  
Protective Effects ◽  
Tnf Α ◽  
Apoptotic Pathways ◽  
Induced Apoptosis ◽  
Factor Α

Fas ligand (CD95L) and tumor necrosis factor-α (TNF-α) are pivotal inducers of hepatocyte apoptosis. Uncontrolled activation of these two systems is involved in several forms of liver injury. Although the broad antiapoptotic action of Bcl-2 and Bcl-xL has been clearly established in various apoptotic pathways, their ability to inhibit the Fas/CD95- and TNF-α-mediated apoptotic signal has remained controversial. We have demonstrated that the expression of BCL-2 in hepatocytes protects them against Fas-induced fulminant hepatitis in transgenic mice. The present study shows that transgenic mice overexpressing[Formula: see text]in hepatocytes are also protected from Fas-induced apoptosis in a dose-dependent manner. Bcl-xL and Bcl-2 were protective without any change in the level of endogenous[Formula: see text]or Bax and inhibited hepatic caspase-3-like activity. In vivo injection of TNF-α caused massive apoptosis and death only when transcription was inhibited. Under these conditions,[Formula: see text]mice were partially protected from liver injury and death but PK-BCL-2 mice were not. A similar differential protective effect of Bcl-xL and Bcl-2 transgenes was observed when Fas/CD95 was activated and transcription blocked. These results suggest that apoptosis triggered by activation of both Fas/CD95 and TNF-α receptors is to some extent counteracted by the transcription-dependent protective effects, which are essential for the antiapoptotic activity of Bcl-2 but not of Bcl-xL. Therefore, Bcl-xL and Bcl-2 appear to have different antiapoptotic effects in the liver whose characterization could facilitate their use to prevent the uncontrolled apoptosis of hepatocytes.

Tumor necrosis factor-α and ceramide induce cell death through different mechanisms in rat mesangial cells

1999 ◽  
Vol 276 (3) ◽  
pp. F390-F397 ◽  
Author(s):  
Yan-Lin Guo ◽  
Baobin Kang ◽  
Li-Jun Yang ◽  
John R. Williamson
Keyword(s):  
Cell Death ◽  
Protein Kinase ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Mesangial Cells ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Factor Α ◽  
Necrosis Factor

It has been proposed that ceramide acts as a cellular messenger to mediate tumor necrosis factor-α (TNF-α)-induced apoptosis. Based on this hypothesis, it was postulated that resistance of some cells to TNF-α cytotoxicity was due to an insufficient production of ceramide on stimulation by TNF-α. The present study was initiated to investigate whether this was the case in mesangial cells, which normally are insensitive to TNF-α-induced apoptosis. Our results indicate that although C2ceramide was toxic to mesangial cells, the cell death it induced differed both morphologically and biochemically from that induced by TNF-α in the presence of cycloheximide (CHX). The most apparent effect of C2ceramide was to cause cells to swell, followed by disruption of the cell membrane. It is evident that C2ceramide caused cell death by necrosis, whereas TNF-α in the presence of CHX killed the cells by apoptosis. C2ceramide did not mimic the effects of TNF-α on the activation of c-Jun NH2-terminal protein kinase and nuclear factor-κB transcription factor. Although mitogen-activated protein kinase [extracellular signal-related kinase (ERK)] was activated by both C2ceramide and TNF-α, such activation appeared to be mediated by different mechanisms as judged from the kinetics of ERK activation. Furthermore, the cleavage of cytosolic phospholipase A2during cell death induced by C2ceramide and by TNF-α in the presence of CHX showed distinctive patterns. The present study provides evidence that apoptosis and necrosis use distinctive signaling machinery to cause cell death.

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.

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 Isoorientin Inhibits Amyloid β25–35-Induced Neuronal Inflammation in BV2 Cells by Blocking the NF-κB Signaling Pathway

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 7056
Author(s):  
Buyun Kim ◽  
Ki Yong Lee ◽  
Byoungduck Park
Keyword(s):  
Neurodegenerative Disorder ◽  
Drug Candidate ◽  
Therapeutic Drug ◽  
Treatment And Prevention ◽  
Bv2 Cells ◽  
Tnf Α ◽  
Underlying Mechanisms ◽  
Induced Apoptosis ◽  
Factor Α ◽  
The Brain

Alzheimer’s disease (AD) is a severe neurodegenerative disorder. AD is pathologically characterized by the formation of intracellular neurofibrillary tangles, and extracellular amyloid plaques which were comprised of amyloid-beta (Aβ) peptides. Aβ induces neurodegeneration by activating microglia, which triggers neurotoxicity by releasing various inflammatory mediators and reactive oxygen species (ROS). Nuclear factor-kappa B (NF-κB) is expressed in human tissues including the brain and plays an important role in Aβ-mediated neuronal inflammation. Thus, the identification of molecules that inhibit the NF-κB pathway is considered an attractive strategy for the treatment and prevention of AD. Isoorientin (3′,4′,5,7-Tetrahydroxy-6-C-glucopyranosyl flavone; ISO), which can be extracted from several plant species, such as Philostachys and Patrinia is known to have various pharmacological activities such as anticancer, antioxidant, and antibacterial activity. However, the effect of ISO on Aβ-mediated inflammation and apoptosis in the brain has yet to be elucidated. In the present study, we investigated whether ISO regulated Aβ-induced neuroinflammation in microglial cells and further explored the underlying mechanisms. Our results showed that ISO inhibited the expression of iNOS and COX-2 induced by Aβ25–35. And, it inhibited the secretion of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). In addition, ISO reduced the ROS production in Aβ25–35-induced BV2 cells and inhibited NF-κB activation. Furthermore, ISO blocked Aβ25–35-induced apoptosis of BV2 cells. Based on these findings, we suggest that ISO represents a promising therapeutic drug candidate for the treatment and prevention of AD.

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