scholarly journals Expression of programmed cell death 5 protein inhibits progression of lung carcinoma in vitro and in vivo via the mitochondrial apoptotic pathway

2014 ◽  
Vol 10 (4) ◽  
pp. 2059-2064 ◽  
Author(s):  
SHINING XU ◽  
GANG SUI ◽  
LEI YUAN ◽  
ZHIQIANG ZOU
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Lung Carcinoma ◽  
Apoptotic Pathway ◽  
Mitochondrial Apoptotic Pathway ◽  
Programmed Cell Death 5

scholarly journals Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2

2012 ◽  
Vol 209 (6) ◽  
pp. 1201-1217 ◽  
Author(s):  
Tadashi Yokosuka ◽  
Masako Takamatsu ◽  
Wakana Kobayashi-Imanishi ◽  
Akiko Hashimoto-Tane ◽  
Miyuki Azuma ◽  
...  
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Programmed Cell Death ◽  
T Cell Activation ◽  
Cell Activation ◽  
Tyrosine Phosphatase ◽  
Cell Receptor ◽  
Programmed Cell Death 1

Programmed cell death 1 (PD-1) is a negative costimulatory receptor critical for the suppression of T cell activation in vitro and in vivo. Single cell imaging elucidated a molecular mechanism of PD-1–mediated suppression. PD-1 becomes clustered with T cell receptors (TCRs) upon binding to its ligand PD-L1 and is transiently associated with the phosphatase SHP2 (Src homology 2 domain–containing tyrosine phosphatase 2). These negative costimulatory microclusters induce the dephosphorylation of the proximal TCR signaling molecules. This results in the suppression of T cell activation and blockade of the TCR-induced stop signal. In addition to PD-1 clustering, PD-1–TCR colocalization within microclusters is required for efficient PD-1–mediated suppression. This inhibitory mechanism also functions in PD-1hi T cells generated in vivo and can be overridden by a neutralizing anti–PD-L1 antibody. Therefore, PD-1 microcluster formation is important for regulation of T cell activation.

scholarly journals The Importance of Exosomal PD-L1 in Cancer Progression and Its Potential as a Therapeutic Target

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3247
Author(s):  
Lingxiao Ye ◽  
Zhengxin Zhu ◽  
Xiaochuan Chen ◽  
Haoran Zhang ◽  
Jiaqi Huang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cancer Progression ◽  
T Cell Activation ◽  
Cell Activation ◽  
Immune Escape ◽  
Tumor Treatment

Binding of programmed cell death ligand 1 (PD-L1) to its receptor programmed cell death protein 1 (PD-1) can lead to the inactivation of cytotoxic T lymphocytes, which is one of the mechanisms for immune escape of tumors. Immunotherapy based on this mechanism has been applied in clinic with some remaining issues such as drug resistance. Exosomal PD-L1 derived from tumor cells is considered to play a key role in mediating drug resistance. Here, the effects of various tumor-derived exosomes and tumor-derived exosomal PD-L1 on tumor progression are summarized and discussed. Researchers have found that high expression of exosomal PD-L1 can inhibit T cell activation in in vitro experiments, but the function of exosomal PD-L1 in vivo remains controversial. In addition, the circulating exosomal PD-L1 has high potential to act as an indicator to evaluate the clinical effect. Moreover, therapeutic strategy targeting exosomal PD-L1 is discussed, such as inhibiting the biogenesis or secretion of exosomes. Besides, some specific methods based on the strategy of inhibiting exosomes are concluded. Further study of exosomal PD-L1 may provide an effective and safe approach for tumor treatment, and targeting exosomal PD-L1 by inhibiting exosomes may be a potential method for tumor treatment.

scholarly journals C-phycocyanin from Limnothrix Species KNUA002 Alleviates Cisplatin-Induced Ototoxicity by Blocking the Mitochondrial Apoptotic Pathway in Auditory Cells

Marine Drugs ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 235 ◽  
Author(s):  
Ye-Ri Kim ◽  
Jeong-Mi Do ◽  
Kyung Hee Kim ◽  
Alexandra R. Stoica ◽  
Seung-Woo Jo ◽  
...  
Keyword(s):  
Organ Of Corti ◽  
Experimental Models ◽  
Common Side Effect ◽  
Anticancer Activities ◽  
Apoptotic Pathway ◽  
Mitochondrial Apoptotic Pathway ◽  
Anticancer Chemotherapy ◽  
Ros Accumulation

Ototoxicity, or adverse pharmacological effects on the inner ear or auditory nerve, is a common side effect of cisplatin, a platinum-based drug widely used in anticancer chemotherapy. Although the incidence of ototoxicity is high among patients that receive cisplatin therapy, there is currently no effective treatment for it. The generation of excessive reactive oxygen species (ROS) is considered to be the major cause of cisplatin-induced ototoxicity. C-phycocyanin (C-PC), a blue phycobiliprotein found in cyanobacteria and red algae, has antioxidant and anticancer activities in different experimental models in vitro and in vivo. Thus, we tested the ability of C-PC from Limnothrix sp. KNUA002 to protect auditory cells from cisplatin-induced ototoxicity in vitro. Pretreatment with C-PC from Limnothrix sp. KNUA002 inhibited apoptosis and protected mitochondrial function by preventing ROS accumulation in cisplatin-treated House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, a mouse auditory cell line. Cisplatin increased the expression of Bax and reduced the expression of Bcl-2, which activate and inhibit, respectively, the mitochondrial apoptotic pathway in response to oxidative stress. Pretreatment with C-PC prior to cisplatin treatment caused the Bax and Bcl-2 levels to stay close to the levels in untreated control cells. Our results suggest that C-PC from Limnothrix sp. KNUA002 protects cells against cisplatin-induced cytotoxicity by inhibiting the mitochondrial apoptotic pathway.

scholarly journals Treatment of melanoma cells with the synthetic retinoid CD437 induces apoptosis via activation of AP-1 in vitro, and causes growth inhibition in xenografts in vivo.

1996 ◽  
Vol 135 (6) ◽  
pp. 1889-1898 ◽  
Author(s):  
D Schadendorf ◽  
M A Kern ◽  
M Artuc ◽  
H L Pahl ◽  
T Rosenbach ◽  
...  
Keyword(s):  
Cell Death ◽  
Malignant Melanoma ◽  
Programmed Cell Death ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Mrna Levels ◽  
Synthetic Retinoid ◽  
Human Melanoma Cells

Human malignant melanoma is notoriously resistant to pharmacological modulation. We describe here for the first time that the synthetic retinoid CD437 has a strong dose-dependent antiproliferative effect on human melanoma cells (IC50: 5 x 10(-6) M) via the induction of programmed cell death, as judged by analysis of cell morphology, electron microscopical features, and DNA fragmentation. Programmed cell death was preceded by a strong activation of the AP-1 complex in CD437-treated cells as demonstrated by gel retardation and chloramphenicol transferase (CAT) assays. Northern blot analysis showed a time-dependent increase in the expression of c-fos and c-jun encoding components of AP-1, whereas bcl-2 and p53 mRNA levels remained constant. CD437 also exhibited a strong growth inhibitory effect on MeWo melanoma cells in a xenograft model. In tissue sections of CD437-treated MeWo tumors from these animals, apoptotic melanoma cells and c-fos overexpressing cells were colocalized by TdT-mediated deoxyuridine triphosphate-digoxigenin nick end labeling (TUNEL) staining and in situ hybridization. Taken together, this report identifies CD437 as a retinoid that activates and upregulates the transcription factor AP-1, leading eventually to programmed cell death of exposed human melanoma cells in vitro and in vivo. Further studies are needed to evaluate whether synthetic retinoids such as CD437 represent a new class of retinoids, which may open up new ways to a more effective therapy of malignant melanoma.

scholarly journals Novel cucurmosin‐based immunotoxin targeting programmed cell death 1‐ligand 1 with high potency against human tumor in vitro and in vivo

2020 ◽  
Vol 111 (9) ◽  
pp. 3184-3194
Author(s):  
Caiyun Zhang ◽  
Jiani Xiong ◽  
Yinxiang Lan ◽  
Jingyu Wu ◽  
Chengyan Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Human Tumor ◽  
High Potency ◽  
Programmed Cell Death 1

scholarly journals Up-regulation of MicroRNA-21 Mediates Isoflurane-induced Protection of Cardiomyocytes

2015 ◽  
Vol 122 (4) ◽  
pp. 795-805 ◽  
Author(s):  
Jessica M. Olson ◽  
Yasheng Yan ◽  
Xiaowen Bai ◽  
Zhi-Dong Ge ◽  
Mingyu Liang ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Messenger Rna ◽  
Functional Role ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cell Death Protein

Abstract Background: Anesthetic cardioprotection reduces myocardial infarct size after ischemia–reperfusion injury. Currently, the role of microRNA in this process remains unknown. MicroRNAs are short, noncoding nucleotide sequences that negatively regulate gene expression through degradation or suppression of messenger RNA. In this study, the authors uncovered the functional role of microRNA-21 (miR-21) up-regulation after anesthetic exposure. Methods: MicroRNA and messenger RNA expression changes were analyzed by quantitative real-time polymerase chain reaction in cardiomyocytes after exposure to isoflurane. Lactate dehydrogenase release assay and propidium iodide staining were conducted after inhibition of miR-21. miR-21 target expression was analyzed by Western blot. The functional role of miR-21 was confirmed in vivo in both wild-type and miR-21 knockout mice. Results: Isoflurane induces an acute up-regulation of miR-21 in both in vivo and in vitro rat models (n = 6, 247.8 ± 27.5% and 258.5 ± 9.0%), which mediates protection to cardiomyocytes through down-regulation of programmed cell death protein 4 messenger RNA (n = 3, 82.0 ± 4.9% of control group). This protective effect was confirmed by knockdown of miR-21 and programmed cell death protein 4 in vitro. In addition, the protective effect of isoflurane was abolished in miR-21 knockout mice in vivo, with no significant decrease in infarct size compared with nonexposed controls (n = 8, 62.3 ± 4.6% and 56.2 ± 3.2%). Conclusions: The authors demonstrate for the first time that isoflurane mediates protection of cardiomyocytes against oxidative stress via an miR-21/programmed cell death protein 4 pathway. These results reveal a novel mechanism by which the damage done by ischemia/reperfusion injury may be decreased.

Biochemical analysis of programmed cell death during premeiotic stages of spermatogenesis in vivo and in vitro

1995 ◽  
Vol 16 (2) ◽  
pp. 140-147 ◽  
Author(s):  
Gloria V. Callard ◽  
Joan C. Jorgensen ◽  
J. Michael Redding
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Biochemical Analysis

scholarly journals Human Monocyte Recognition of Adenosine-Based Cyclic Dinucleotides Unveils the A2a GαsProtein-Coupled Receptor Tonic Inhibition of Mitochondrially Induced Cell Death

2014 ◽  
Vol 35 (2) ◽  
pp. 479-495 ◽  
Author(s):  
Marie Tosolini ◽  
Frédéric Pont ◽  
Delphine Bétous ◽  
Emmanuel Ravet ◽  
Laetitia Ligat ◽  
...  
Keyword(s):  
Cell Death ◽  
Mammalian Cells ◽  
Mitochondrial Permeability Transition ◽  
Human Monocyte ◽  
Inverse Agonist ◽  
Apoptotic Pathway ◽  
Cyclic Dinucleotides ◽  
Agonist Ligands

Cyclic dinucleotides are important messengers for bacteria and protozoa and are well-characterized immunity alarmins for infected mammalian cells through intracellular binding to STING receptors. We sought to investigate their unknown extracellular effects by adding cyclic dinucleotides to the culture medium of freshly isolated human blood cellsin vitro. Here we report that adenosine-containing cyclic dinucleotides induce the selective apoptosis of monocytes through a novel apoptotic pathway. We demonstrate that these compounds are inverse agonist ligands of A2a, a Gαs-coupled adenosine receptor selectively expressed by monocytes. Inhibition of monocyte A2a by these ligands induces apoptosis through a mechanism independent of that of the STING receptors. The blockade of basal (adenosine-free) signaling from A2a inhibits protein kinase A (PKA) activity, thereby recruiting cytosolic p53, which opens the mitochondrial permeability transition pore and impairs mitochondrial respiration, resulting in apoptosis. A2a antagonists and inverse agonist ligands induce apoptosis of human monocytes, while A2a agonists are antiapoptotic.In vivo, we used a mock developing human hematopoietic system through NSG mice transplanted with human CD34+cells. Treatment with cyclic di-AMP selectively depleted A2a-expressing monocytes and their precursors via apoptosis. Thus, monocyte recognition of cyclic dinucleotides unravels a novel proapoptotic pathway: the A2a Gαsprotein-coupled receptor (GPCR)-driven tonic inhibitory signaling of mitochondrion-induced cell death.

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