scholarly journals Antiapoptotic Effect of Acetylcholine in Fas-Induced Apoptosis in Human Keratocytes

2016 ◽  
Vol 57 (14) ◽  
pp. 5892 ◽  
Author(s):  
Marta Sloniecka ◽  
Ludvig J. Backman ◽  
Patrik Danielson
Keyword(s):  
Antiapoptotic Effect ◽  
Induced Apoptosis ◽  
Human Keratocytes

scholarly journals The Antiapoptotic Effect of BHV-1 in Sorbitol-induced Apoptosis in MDBK Cells

2001 ◽  
Vol 1 ◽  
pp. 35-35
Author(s):  
G. Marfè ◽  
L. De Martino ◽  
C. Di Stefano ◽  
G. Iovane
Keyword(s):  
Antiapoptotic Effect ◽  
Mdbk Cells ◽  
Induced Apoptosis

Triggering of CD40 Antigen Inhibits Fludarabine-Induced Apoptosis in B Chronic Lymphocytic Leukemia Cells

Blood ◽  
1998 ◽  
Vol 92 (3) ◽  
pp. 990-995 ◽  
Author(s):  
Maria Fiammetta Romano ◽  
Annalisa Lamberti ◽  
Pierfrancesco Tassone ◽  
Fiorella Alfinito ◽  
Silvia Costantini ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Consensus Sequence ◽  
Significant Proportion ◽  
Lymphocytic Leukemia ◽  
Antiapoptotic Effect ◽  
Apoptotic Effect ◽  
American Society ◽  
Induced Apoptosis ◽  
Decoy Oligonucleotide

Abstract We analyzed the effect of CD40 triggering on the fludarabine-induced apoptosis of B chronic lymphocytic leukemia (B-CLL) cells. Peripheral blood samples obtained from 15 patients were incubated with fludarabine in the absence or the presence of the anti-CD40 monoclonal antibody (MoAb) G28-5. In 12 patients a significant proportion of apoptotic cells, ranging from 22% to 38% (mean ± SE: 28.5 ± 1.6), were detected after 3 days of culture. In 9 of these samples, the addition of G28-5 reduced apoptosis by at least 30.1% and by 57.1% ± 7.8% on average (P = .0077). Because the CD40 antigen activates NF-κB/Rel transcription factors in B cells, and NF-κB/Rel complexes can inhibit cell apoptosis, we investigated whether the antiapoptotic effect of G28-5, in our system, could be related to modulation of NF-κB/Rel activity. As expected, B-CLL cells displayed significant levels of nuclear NF-κB/Rel activity; p50, RelA, and c-Rel components of the NF-κB/Rel protein family were identified in these complexes. After exposure to fludarabine, NF-κB/Rel complexes were decreased in the nuclei. The addition of G28-5 upregulated the NF-κB/Rel levels. To determine the involvement of NF-κB/Rel activity in the G28-5–mediated inhibition of apoptosis, we blocked the transcription factor with a decoy oligonucleotide, corresponding to the NF-κB/Rel consensus sequence. Cells incubated with the anti-CD40 MoAb in the presence of the decoy oligonucleotide but not a control oligonucleotide displayed a complete impairment of the G28-5 antiapoptotic effect, indicating that NF-κB/Rel activity was required for the inhibition of apoptosis. These results suggest that CD40 triggering in vivo could counteract the apoptotic effect of fludarabine on B-CLL cells and that its neutralization, or the use of NF-κB/Rel inhibitors, could improve the therapeutic effect of fludarabine. © 1998 by The American Society of Hematology.

scholarly journals IAP Suppression of Apoptosis Involves Distinct Mechanisms: the TAK1/JNK1 Signaling Cascade and Caspase Inhibition

2002 ◽  
Vol 22 (6) ◽  
pp. 1754-1766 ◽  
Author(s):  
M. Germana Sanna ◽  
Jean da Silva Correia ◽  
Odile Ducrey ◽  
Jongdae Lee ◽  
Ken Nomoto ◽  
...  
Keyword(s):  
Signaling Cascade ◽  
Inhibitor Of Apoptosis ◽  
Alternative Mechanism ◽  
Caspase Activity ◽  
Selective Activation ◽  
Antiapoptotic Effect ◽  
Caspase Inhibition ◽  
Tnf Α ◽  
Antiapoptotic Activity ◽  
Induced Apoptosis

ABSTRACT The antiapoptotic properties of the inhibitor of apoptosis (IAP) family of proteins have been linked to caspase inhibition. We have previously described an alternative mechanism of XIAP inhibition of apoptosis that depends on the selective activation of JNK1. Here we report that two other members of the IAP family, NAIP and ML-IAP, both activate JNK1. Expression of catalytically inactive JNK1 blocks NAIP and ML-IAP protection against ICE- and TNF-α-induced apoptosis, indicating that JNK1 activation is necessary for the antiapoptotic effect of these proteins. The MAP3 kinase, TAK1, appears to be an essential component of this antiapoptotic pathway since IAP-mediated activation of JNK1, as well as protection against TNF-α- and ICE-induced apoptosis, is inhibited when catalytically inactive TAK1 is expressed. In addition, XIAP, NAIP, and JNK1 bind to TAK1. Importantly, expression of catalytically inactive TAK1 did not affect XIAP inhibition of caspase activity. These data suggest that XIAP's antiapoptotic activity is achieved by two separate mechanisms: one requiring TAK1-dependent JNK1 activation and the second involving caspase inhibition.

Triggering of CD40 Antigen Inhibits Fludarabine-Induced Apoptosis in B Chronic Lymphocytic Leukemia Cells

Blood ◽  
1998 ◽  
Vol 92 (3) ◽  
pp. 990-995 ◽  
Author(s):  
Maria Fiammetta Romano ◽  
Annalisa Lamberti ◽  
Pierfrancesco Tassone ◽  
Fiorella Alfinito ◽  
Silvia Costantini ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Consensus Sequence ◽  
Significant Proportion ◽  
Lymphocytic Leukemia ◽  
Antiapoptotic Effect ◽  
Apoptotic Effect ◽  
American Society ◽  
Induced Apoptosis ◽  
Decoy Oligonucleotide

We analyzed the effect of CD40 triggering on the fludarabine-induced apoptosis of B chronic lymphocytic leukemia (B-CLL) cells. Peripheral blood samples obtained from 15 patients were incubated with fludarabine in the absence or the presence of the anti-CD40 monoclonal antibody (MoAb) G28-5. In 12 patients a significant proportion of apoptotic cells, ranging from 22% to 38% (mean ± SE: 28.5 ± 1.6), were detected after 3 days of culture. In 9 of these samples, the addition of G28-5 reduced apoptosis by at least 30.1% and by 57.1% ± 7.8% on average (P = .0077). Because the CD40 antigen activates NF-κB/Rel transcription factors in B cells, and NF-κB/Rel complexes can inhibit cell apoptosis, we investigated whether the antiapoptotic effect of G28-5, in our system, could be related to modulation of NF-κB/Rel activity. As expected, B-CLL cells displayed significant levels of nuclear NF-κB/Rel activity; p50, RelA, and c-Rel components of the NF-κB/Rel protein family were identified in these complexes. After exposure to fludarabine, NF-κB/Rel complexes were decreased in the nuclei. The addition of G28-5 upregulated the NF-κB/Rel levels. To determine the involvement of NF-κB/Rel activity in the G28-5–mediated inhibition of apoptosis, we blocked the transcription factor with a decoy oligonucleotide, corresponding to the NF-κB/Rel consensus sequence. Cells incubated with the anti-CD40 MoAb in the presence of the decoy oligonucleotide but not a control oligonucleotide displayed a complete impairment of the G28-5 antiapoptotic effect, indicating that NF-κB/Rel activity was required for the inhibition of apoptosis. These results suggest that CD40 triggering in vivo could counteract the apoptotic effect of fludarabine on B-CLL cells and that its neutralization, or the use of NF-κB/Rel inhibitors, could improve the therapeutic effect of fludarabine. © 1998 by The American Society of Hematology.

Morphine mimics the antiapoptotic effect of preconditioning via an Ins(1,4,5)P3 signaling pathway in rat ventricular myocytes

2005 ◽  
Vol 288 (1) ◽  
pp. H83-H88 ◽  
Author(s):  
Stéphanie Barrère-Lemaire ◽  
Nicolas Combes ◽  
Catherine Sportouch-Dukhan ◽  
Sylvain Richard ◽  
Joël Nargeot ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Signaling Pathway ◽  
Dna Fragmentation ◽  
Ventricular Myocytes ◽  
Neonatal Rat ◽  
Cytochrome C Release ◽  
Rat Cardiomyocytes ◽  
Rat Ventricular Myocytes ◽  
Antiapoptotic Effect ◽  
Induced Apoptosis

Morphine has cardioprotective effects against ischemic-reperfusion injuries. This study investigates whether morphine could mimic the antiapoptotic effect of preconditioning using a model of cultured neonatal rat cardiomyocytes subjected to metabolic inhibition (MI). To quantify MI-induced apoptosis, DNA fragmentation and mitochondrial cytochrome c release levels were measured by ELISA. MI-dependent DNA fragmentation was prevented by both Z-VAD-fmk (20 μM), a pan-caspase inhibitor, and cyclosporine A (CsA; 5 μM), a mitochondrial pore transition blocker, added during MI (36% and 54% decrease, respectively). MI-dependent cytochrome c release was not blocked by Z-VAD-fmk but was decreased (38%) by CsA during MI. Metabolic preconditioning (MIP) and preconditioning with morphine (1 μM) were also assessed. MI-dependent DNA fragmentation and cytochrome c release were prevented by MIP (40% and 45% decrease, respectively) and morphine (34% and 45%, respectively). The antiapoptotic effect of morphine was abolished by naloxone (10 nM), a nonselective opioid receptor antagonist, or xestospongin C (XeC, 400 nM), an inhibitor of inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3]-mediated Ca2+ release. Ca2+ preconditioning, induced by increasing extracellular Ca2+ from 1.8 to 3.3 mM, mimicked the antiapoptotic effect of morphine on DNA fragmentation (24% decrease) and cytochrome c release (57% decrease). This effect mediated by extracellular Ca2+ was also abolished by XeC. Measurements of intracellular Ca2+ concentration using fura-2 microspectrofluorimetry showed that morphine induces Ins(1,4,5)P3-dependent Ca2+ transients abolished by 2-aminoethoxydiphenyl borate (2-APB), a cell-permeable Ins(1,4,5)P3 antagonist. These results suggest that morphine preconditioning prevents simulated ischemia-reperfusion-induced apoptosis via an Ins(1,4,5)P3 signaling pathway in rat ventricular myocytes.

scholarly journals Cardioprotective effect of adiponectin is partially mediated by its AMPK-independent antinitrative action

2009 ◽  
Vol 297 (2) ◽  
pp. E384-E391 ◽  
Author(s):  
Yajing Wang ◽  
Ling Tao ◽  
Yuexin Yuan ◽  
Wayne Bond Lau ◽  
Rong Li ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Metabolic Regulation ◽  
Antioxidant Property ◽  
Dominant Negative ◽  
Globular Domain ◽  
Activation Effect ◽  
Antiapoptotic Effect ◽  
Signaling Axis ◽  
Induced Apoptosis ◽  
Endothelial Nitric Oxide

Adiponectin (APN) exerts its metabolic regulation largely through AMP-dependent protein kinase (AMPK). However, the role of AMPK in APN's antiapoptotic effect in ischemic-reperfused (I/R) adult cardiomyocytes remains incompletely understood. The present study was designed to determine the involvement of AMPK in the antiapoptotic signaling of APN. Cardiomyocytes from adult male mice overexpressing a dominant-negative α2-subunit of AMPK (AMPK-DN) or wild-type (WT) littermates were subjected to simulated I/R (SI/R) and pretreated with 2 μg/ml globular domain of APN (gAPN) or vehicle. SI/R-induced cardiomyocyte apoptosis was modestly increased in AMPK-DN cardiomyocytes ( P < 0.05). Treatment with gAPN significantly reduced SI/R-induced apoptosis in WT cardiomyocytes as well as in AMPK-DN cardiomyocytes, indicating that the antiapoptotic effect of gAPN is partially AMPK independent. Furthermore, gAPN-induced endothelial nitric oxide synthase (eNOS) phosphorylation was significantly reduced in AMPK-DN cardiomyocytes, suggesting that the APN-eNOS signaling axis is impaired in AMPK-DN cardiomyocytes. Additional experiments demonstrated that treatment of AMPK-DN cardiomyocytes with gAPN reduced SI/R-induced NADPH oxidase overexpression, decreased superoxide generation, and blocked peroxynitrite formation to the same extent as that observed in WT cardiomyocytes. Collectively, our present study demonstrated that although the metabolic and eNOS activation effect of APN is largely mediated by AMPK, the superoxide-suppressing effect of APN is not mediated by AMPK, and this AMPK-independent antioxidant property of APN increased nitric oxide bioavailability and exerted significant antiapoptotic effect.

Rosiglitazone inhibits high glucose-induced apoptosis in human umbilical vein endothelial cells through the PI3K/Akt/eNOS pathway

2009 ◽  
Vol 87 (7) ◽  
pp. 549-555 ◽  
Author(s):  
Jing Wu ◽  
Min-Xiang Lei ◽  
Xiao-Yun Xie ◽  
Lan Liu ◽  
Yan-Mei She ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Umbilical Vein ◽  
No Production ◽  
Human Umbilical Vein ◽  
Pi3k Inhibitor Ly294002 ◽  
Antiapoptotic Effect ◽  
Induced Apoptosis ◽  
Umbilical Vein Endothelial Cells ◽  
Endothelial Nitric Oxide

Previous studies have shown that the phosphatidylinositol 3-kinase / Akt / endothelial nitric oxide synthase / NO (PI3K/Akt/eNOS/NO) pathway is involved in high glucose-induced endothelial cell apoptosis and rosiglitazone has a protective effect on endothelium. In the present study, we investigated the antiapoptotic effect of rosiglitazone on human umbilical vein endothelial cells (HUVECs) exposed to high glucose and explored its possible mechanism. Treatment of high glucose (33 mmol/L) for 48 h significantly induced the apoptosis of HUVECs, concomitantly with increased caspase-3 activity. High glucose treatment also decreased Akt and eNOS phosphorylation levels with subsequent NO production. All these alterations induced by high glucose were attenuated by rosiglitazone (1 µmol/L). Interestingly, the antiapoptotic effect of rosiglitazone was inhibited by PI3K inhibitor (LY294002, wortmannin) or eNOS inhibitor NG-l-nitro-arginine methyl ester (l-NAME). The reverse effects of rosiglitazone on phosphorylation of Akt and eNOS with subsequent NO production were also inhibited by LY294002, wortmannin or l-NAME, respectively. These findings suggest that rosiglitazone inhibits high glucose-induced apoptosis in HUVECs through the PI3K/Akt/eNOS pathway.

scholarly journals Neisseria gonorrhoeae Infection Protects Human Endocervical Epithelial Cells from Apoptosis via Expression of Host Antiapoptotic Proteins

2009 ◽  
Vol 77 (9) ◽  
pp. 3602-3610 ◽  
Author(s):  
S. A. Follows ◽  
J. Murlidharan ◽  
P. Massari ◽  
L. M. Wetzler ◽  
C. A. Genco
Keyword(s):  
Epithelial Cells ◽  
Neisseria Gonorrhoeae ◽  
Immune Evasion ◽  
Transmitted Disease ◽  
Host Cells ◽  
Microbial Pathogens ◽  
Antiapoptotic Effect ◽  
Antiapoptotic Proteins ◽  
Protein Levels ◽  
Induced Apoptosis

ABSTRACT Several microbial pathogens can modulate the host apoptotic response to infection, which may contribute to immune evasion. Various studies have reported that infection with the sexually transmitted disease pathogen Neisseria gonorrhoeae can either inhibit or induce apoptosis. N. gonorrhoeae infection initiates at the mucosal epithelium, and in women, cells from the ectocervix and endocervix are among the first host cells encountered by this pathogen. In this study, we defined the antiapoptotic effect of N. gonorrhoeae infection in human endocervical epithelial cells (End/E6E7 cells). We first established that N. gonorrhoeae strain FA1090B failed to induce cell death in End/E6E7 cells. Subsequently, we demonstrated that stimulation with N. gonorrhoeae protected these cells from staurosporine (STS)-induced apoptosis. Importantly, only End/E6E7 cells incubated with live bacteria and in direct association with N. gonorrhoeae were protected from STS-induced apoptosis, while heat-killed and antibiotic-killed bacteria failed to induce protection. Stimulation of End/E6E7 cells with live N. gonorrhoeae induced NF-κB activation and resulted in increased gene expression of the NF-κB-regulated antiapoptotic genes bfl-1, cIAP-2, and c-FLIP. Furthermore, cIAP-2 protein levels also increased in End/E6E7 cells incubated with gonococci. Collectively, our results indicate that the antiapoptotic effect of N. gonorrhoeae in human endocervical epithelial cells results from live infection via expression of host antiapoptotic proteins. Securing an intracellular niche through the inhibition of apoptosis may be an important mechanism utilized by N. gonorrhoeae for microbial survival and immune evasion in cervical epithelial cells.

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