Establishment of Persistent Infection with HIV-1 Abrogates the Caspase-3-Dependent Apoptotic Signaling Pathway in U937 Cells

1999 ◽  
Vol 247 (2) ◽  
pp. 514-524 ◽  
Author(s):  
Yasuharu Tanaka ◽  
Masanori Kameoka ◽  
Katsuya Ota ◽  
Asako Itaya ◽  
Kazuyoshi Ikuta ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Persistent Infection ◽  
Caspase 3 ◽  
U937 Cells ◽  
Apoptotic Signaling ◽  
Hiv 1

scholarly journals Baicalein Alleviates Osteoarthritis Progression in Mice by Protecting Subchondral Bone and Suppressing Chondrocyte Apoptosis Based on Network Pharmacology

2022 ◽  
Vol 12 ◽  
Author(s):  
Nanxing Yi ◽  
Yilin Mi ◽  
Xiaotong Xu ◽  
Naping Li ◽  
Fan Zeng ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Articular Cartilage ◽  
Signaling Pathway ◽  
Subchondral Bone ◽  
Caspase 3 ◽  
Synovial Inflammation ◽  
Joint Disease ◽  
Network Pharmacology ◽  
Chondrocyte Apoptosis ◽  
Apoptotic Signaling

As life expectancy increases, Osteoarthritis (OA) is becoming a more frequently seen chronic joint disease. The main characteristics of OA are loss of articular cartilage, subchondral bone sclerosis, and synovial inflammation. Baicalein (Bai), a traditional Chinese medicine extracted from Scutellaria baicalensis Georgi, has been demonstrated to exert notable anti-inflammatory effects in previous studies, suggesting its potential effect in the treatment of OA. In this study, we first predicted the action targets of Bai, mapped target genes related to OA, identified potential anti-OA targets for Bai, performed gene ontology (GO) enrichment, and KEGG signaling pathway analyses of the action targets, and analyzed the molecular docking of key Bai targets. Additionally, the effect and potential mechanism of Bai against OA were verified in mouse knee OA models induced by destabilized medial meniscus (DMM) surgery. GO and KEGG analyses showed that 19 anti-OA targets were mainly involved in the response to oxidative stress, the response to hypoxia and apoptosis, and the PI3K-Akt and p53 signaling pathways. Molecular docking results indicated that BAX, BCL 2, and Caspase 3 enriched in the apoptotic signaling pathway have high binding affinity with Bai. Validation experiments showed that Bai can significantly attenuate the loss of articular cartilage (OARSI score), suppress synovial inflammation (synovitis score), and ameliorate subchondral bone resorption measured by micro-CT. In addition, Bai notably inhibited the expression of apoptosis-related proteins in articular cartilage (BAX, BCL 2, and Caspase 3). By combining network pharmacology with experimental validation, our study identifies and verifies the importance of the apoptotic signaling pathway in the treatment of OA by Bai. Bai may have promising application and potential therapeutic value in OA treatment.

scholarly journals Endoplasmic Reticulum Stress Cooperates in Silica Nanoparticles-Induced Macrophage Apoptosis via Activation of CHOP-Mediated Apoptotic Signaling Pathway

2019 ◽  
Vol 20 (23) ◽  
pp. 5846 ◽  
Author(s):  
Fenglei Chen ◽  
Jiaqi Jin ◽  
Jiahui Hu ◽  
Yujing Wang ◽  
Zhiyu Ma ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Raw 264.7 ◽  
Apoptotic Signaling ◽  
Macrophage Cells ◽  
Raw 264.7 Macrophage ◽  
Raw 264.7 Macrophage Cells

While silica nanoparticles (SiNPs) have wide applications, they inevitably increase atmospheric particulate matter and human exposure to this nanomaterial. Numerous studies have focused on how to disclose SiNP toxicity and on understanding its toxic mechanisms. However, there are few studies in the literature reporting the interaction between endoplasmic reticulum (ER) stress and SiNP exposure, and the corresponding detailed mechanisms have not been clearly determined. In this study, CCK-8 and flow cytometry assays demonstrated that SiNPs gradually decreased cell viability and increased cell apoptosis in RAW 264.7 macrophage cells in dose- and time-dependent manners. Western blot analysis showed that SiNPs significantly activated ER stress by upregulating GRP78, CHOP, and ERO1α expression. Meanwhile, western blot analysis also showed that SiNPs activated the mitochondrial-mediated apoptotic signaling pathway by upregulating BAD and Caspase-3, and downregulating the BCL-2/BAX ratio. Moreover, 4-phenylbutyrate (4-PBA), an ER stress inhibitor, significantly decreased GRP78, CHOP, and ERO1α expression, and inhibited cell apoptosis in RAW 264.7 macrophage cells. Furthermore, overexpression of CHOP significantly enhanced cell apoptosis, while knockdown of CHOP significantly protected RAW 264.7 macrophage cells from apoptosis induced by SiNPs. We found that the CHOP-ERO1α-caspase-dependent apoptotic signaling pathway was activated by upregulating the downstream target protein ERO1α and caspase-dependent mitochondrial-mediated apoptotic signaling pathway by upregulating Caspase-3 and downregulating the ratio of BCL-2/BAX. In summary, ER stress participated in cell apoptosis induced by SiNPs and CHOP regulated SiNP-induced cell apoptosis, at least partly, via activation of the CHOP-ERO1α-caspase apoptotic signaling pathway in RAW 264.7 macrophage cells.

Targeting Therapy for Resistant Multiple Myeloma with a Novel Inhibitor of NF-KB, NPI-1387.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 640-640
Author(s):  
Dharminder Chauhan ◽  
Ta-Hsiang Chao ◽  
Deli He ◽  
Teru Hideshima ◽  
Laurence Catley ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Caspase 3 ◽  
Luciferase Reporter ◽  
Caspase 8 ◽  
Caspase 9 ◽  
Nuclear Condensation ◽  
Apoptotic Signaling

Abstract Transcription factor NF-KB is linked to growth and survival of multiple myeloma (MM)cells; blockade of NF-KB activity is therefore an attractive therapeutic strategy. Here we describe NPI-1387, a potent inhibitor of NF-KB activation and its effects on MM cells, including those resistant to conventional agents dexamethasone or doxorubicin. Cell-based assays were used to screen a library of 200 semi-synthetic analogs derived from the pimarane diterpene, Acanthoic acid. Among these analogs, NPI-1387 inhibited LPS-induced TNF-A synthesis in the murine macrophage-like RAW 264.7 cells most potently. Importantly, NPI-1387 reduced TNF-A-induced NF-KB activation in a HEK293 NF-KB/luciferase reporter cell line. Therefore additional studies were initiated to define the biological activities in MM. Treatment of MM cells lines (MM.1S, MM.1R, OCI-My5, OPM1, Dox-40) with NPI-1347 for 48h induces a dose-dependent significant (P < 0.004) decrease in cell viability in all cell lines at pharmacologically achievable concentrations (IC50 range 25–40 micromolar). To determine whether NPI-1387-decreased cell viability is due to apoptosis, various MM cell lines were treated at their respective IC50 for 48h; harvested; and analyzed for apoptosis. NPI-1387 triggered significant apoptosis in these cells, as measured by a marked increase in nuclear condensation reflected by dense pattern of DAPI stain under phase contrast microscopy. In contrast, untreated control cells exhibited homogeneous and intact nuclei. Besides nuclear condensation, NPI-1387 triggered proteolytic cleavage of poly (ADP ribose) polymerase (PARP), a hallmark of apoptosis. Examination of purified patient MM cells demonstrated similar results. Notably, NPI-1387 decreases the viability of cells obtained from Bortezomib-refractory MM patient. In contrast, no significant toxicity of NPI-1387 was observed against peripheral blood mononuclear cells from normal healthy donors or CD138− MM patient cells. Moreover, NPI-1387 does not affect the viability of MM patient-derived bone marrow stromal cells (BMSCs). Genetic and biochemical evidence indicates that apoptosis proceeds by two major cell death pathways: an intrinsic pathway that involves mitochondrial membrane permeabilization and release of several apoptogenic factors, followed by caspase-9 activation; and an extrinsic apoptotic signaling pathway that occurs via caspase-8 activation. Both caspase-8 and caspase-9 activate downstream caspase-3. We therefore next examined whether NPI-1387 triggers extrinsic or intrinsic apoptotic signaling pathways. Our results show that NPI-1387 (25 micromolar) induces activation of caspase-8, and caspase-9, followed by caspase-3 cleavage. These data suggest that NPI-1387-triggered MM cell apoptosis predominantly proceeds via caspase-8/caspase-9>>>>caspase-3 signaling pathway. Together, these findings provide the rationale for clinical evaluation of NPI-1387 to induce MM cell killing, overcome drug-resistance, and improve patient outcome in MM.

scholarly journals Fumanjian, a Classic Chinese Herbal Formula, Can Ameliorate the Impairment of Spatial Learning and Memory through Apoptotic Signaling Pathway in the Hippocampus of Rats withAβ1–40-Induced Alzheimer’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Hai-yan Hu ◽  
Zhi-hui Cui ◽  
Hui-qin Li ◽  
Yi-ru Wang ◽  
Xiang Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Learning And Memory ◽  
Ming Dynasty ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Tunel Staining ◽  
Apoptotic Signaling ◽  
Chinese Herbal

Alzheimer’s disease (AD) is the most common form of dementia and lacks disease-altering treatments. Fumanjian (FMJ), a famous classic Chinese herbal prescription for dementia, was first recorded in theComplete Works of Jingyueduring the Ming Dynasty. This study aimed to investigate whether FMJ could prevent cognitive deficit and take neuroprotective effects inAβ1–40-induced rat model through apoptotic signaling pathway. AD model was established by bilateral injection ofAβ1–40into hippocampus in rat. All rats were tested for their capabilities of spatial navigation and memorization by Morris water maze. Apoptosis was tested using TUNEL staining in hippocampus neuronal cells; RT-PCR tested expression of Bcl-2 and Bax mRNA; western blotting tested protein level of cleaved caspase-3. After 14 days of treatment, FMJ significantly improved the escape latency and enhanced platform-cross number compared with theAβ1–40-injected group (P<0.05orP<0.01). FMJ also significantly decreased number of TUNEL-positive neuronal apoptosis and the expressions of Bax and cleaved Caspase-3 and increased the expression of Bcl-2 (P<0.01) compared with AD model group. In conclusion, FMJ exerts a protective effect againstAβ1–40-induced learning and memory deficits and neuronal apoptosis, suggesting that FMJ could be used as a potential therapeutic formula for AD.

The main anthocyanin monomer of Lycium ruthenicum Murray induces apoptosis through the ROS/PTEN/PI3K/Akt/caspase 3 signaling pathway in prostate cancer DU-145 cells

2021 ◽  
Author(s):  
Zhan-Long Li ◽  
Jia Mi ◽  
Lu Lu ◽  
Qing Luo ◽  
Xi Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Lycium Ruthenicum

Pt3G inhibits DU-145 cell proliferation and induces apoptosis through the ROS/PTEN/PI3K/Akt/caspase-3 signaling pathway.

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