The role of human phospholipid scramblases in apoptosis: An overview

Sivagnanam, Ulaganathan; Palanirajan, Santosh Kumar; Gummadi, Sathyanarayana N.

doi:10.1016/j.bbamcr.2017.08.008

Cited by 34 publications

(27 citation statements)

References 129 publications

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“…In addition, rs9814705 and rs1513419 had P values of borderline significance (0.049) for being cis-eQTL of PLSCR1 in lipopolysaccharidestimulated monocytes from healthy individuals 35 . The PLSCR1 gene, located 565 kb away from rs9814705, encodes the transmembrane protein phospholipid scramblase 1, which has been shown to be overexpressed after stimulation with type I interferons, and to play a crucial role in apoptosis 36,37 . This gene has also been identified as a core gene in the host response to tuberculosis in a meta-analysis of transcriptomic data 38 .…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study of Buruli ulcer in rural Benin highlights role of two LncRNAs and the autophagy pathway

et al. 2020

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Buruli ulcer, caused by Mycobacterium ulcerans and characterized by devastating necrotizing skin lesions, is the third mycobacterial disease worldwide. The role of host genetics in susceptibility to Buruli ulcer has long been suggested. We conduct the first genome-wide association study of Buruli ulcer on a sample of 1524 well characterized patients and controls from rural Benin. Two-stage analyses identify two variants located within LncRNA genes: rs9814705 in ENSG00000240095.1 (P = 2.85 × 10 −7 ; odds ratio = 1.80 [1.43-2.27]), and rs76647377 in LINC01622 (P = 9.85 × 10 −8 ; hazard ratio = 0.41 [0.28-0.60]). Furthermore, we replicate the protective effect of allele G of a missense variant located in ATG16L1, previously shown to decrease bacterial autophagy (rs2241880, P = 0.003; odds ratio = 0.31 [0.14-0.68]). Our results suggest LncRNAs and the autophagy pathway as critical factors in the development of Buruli ulcer.

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Section: Discussionmentioning

confidence: 99%

Genome-wide association study of Buruli ulcer in rural Benin highlights role of two LncRNAs and the autophagy pathway

et al. 2020

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“…In future studies, the assays could be modified to image the phagocytosis of apoptotic human red blood cells. Application of a Ca 2+ ionophore, such as A23187, can be used to induce phosphatidylserine externalization 23 , an "eat me" signal and hallmark of early apoptosis 24,25 .…”

Section: Discussionmentioning

confidence: 99%

Time-lapse 3D Imaging of Phagocytosis by Mouse Macrophages

Horsthemke¹,

Wilden²,

Bachg³

et al. 2018

JoVE

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Phagocytosis plays a key role in host defense, as well as in tissue development and maintenance, and involves rapid, receptor-mediated rearrangements of the actin cytoskeleton to capture, envelop and engulf large particles. Although phagocytic receptors, downstream signaling pathways, and effectors, such as Rho GTPases, have been identified, the dynamic cytoskeletal remodeling of specific receptor-mediated phagocytic events remain unclear. Four decades ago, two distinct mechanisms of phagocytosis, exemplified by Fcγ receptor (FcγR)-and complement receptor (CR)-mediated phagocytosis, were identified using scanning electron microscopy. Binding of immunoglobulin G (IgG)opsonized particles to FcγRs triggers the protrusion of thin membrane extensions, which initially form a so-called phagocytic cup around the particle before it becomes completely enclosed and retracted into the cell. In contrast, complement opsonized particles appear to sink into the phagocyte following binding to complement receptors. These two modes of phagocytosis, phagocytic cup formation and sinking in, have become well established in the literature. However, the distinctions between the two modes have become blurred by reports that complement receptor-mediated phagocytosis may induce various membrane protrusions. With the availability of high resolution imaging techniques, phagocytosis assays are required that allow real-time 3D (three dimensional) visualization of how specific phagocytic receptors mediate the uptake of individual particles. More commonly used approaches for the study of phagocytosis, such as end-point assays, miss the opportunity to understand what is happening at the interface of particles and phagocytes. Here we describe phagocytic assays, using time-lapse spinning disk confocal microscopy, that allow 3D imaging of single phagocytic events. In addition, we describe assays to unambiguously image Fcγ receptoror complement receptor-mediated phagocytosis. Video Link The video component of this article can be found at https://www.jove.com/video/57566/ 2. Live-cell imaging of single phagocytic events spanning from particle capture to internalization, combined with genetically modified mouse models, could greatly improve our understanding of how phagocytes capture and ingest particles. One approach could be to use fast atomic force microscopy (AFM) which allows ultra-high resolution (10-20 nm) topographical imaging of living cells. Recently, a fast AFM system 12 has been developed, which is suitable for imaging cell surfaces rapidly with low noise. This technique has the advantage that high-resolution, topographical and mechanical parameters of living cells can be measured at short intervals (seconds), unlike scanning electron microscopy, which necessitates the fixation and critical point drying of cells. Another approach is time-lapse 3D confocal microscopy, which is

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“…Apoptosomes induce apoptosis by activating the downstream executioner caspases, including caspase-3, caspase-6, and caspase-7 [23]. Alternatively, the death ligand activates the death receptor to trigger the extrinsic pathway [24][25][26]. The death-inducing signaling complex activates caspase-8 and -10 [24,26].…”

Section: Introductionmentioning

confidence: 99%

Deoxypodophyllotoxin, a Lignan from Anthriscus sylvestris, Induces Apoptosis and Cell Cycle Arrest by Inhibiting the EGFR Signaling Pathways in Esophageal Squamous Cell Carcinoma Cells

Kwak

Lee

Yoon

et al. 2020

IJMS

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Deoxypodophyllotoxin (DPT) derived from Anthriscus sylvestris (L.) Hoffm has attracted considerable interest in recent years because of its anti-inflammatory, antitumor, and antiviral activity. However, the mechanisms underlying DPT mediated antitumor activity have yet to be fully elucidated in esophageal squamous cell carcinoma (ESCC). We show here that DPT inhibited the kinase activity of epidermal growth factor receptor (EGFR) directly, as well as phosphorylation of its downstream signaling kinases, AKT, GSK-3β, and ERK. We confirmed a direct interaction between DPT and EGFR by pull-down assay using DPT-beads. DPT treatment suppressed ESCC cell viability and colony formation in a time- and dose-dependent manner, as shown by MTT analysis and soft agar assay. DPT also down-regulated cyclin B1 and cdc2 expression to induce G2/M phase arrest of the cell cycle and upregulated p21 and p27 expression. DPT treatment of ESCC cells triggered the release of cytochrome c via loss of mitochondrial membrane potential, thereby inducing apoptosis by upregulation of related proteins. In addition, treatment of KYSE 30 and KYSE 450 cells with DPT increased endoplasmic reticulum stress, reactive oxygen species generation, and multi-caspase activation. Consequently, our results suggest that DPT has the potential to become a new anticancer therapeutic by inhibiting EGFR mediated AKT/ERK signaling pathway in ESCC.

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The role of human phospholipid scramblases in apoptosis: An overview

Cited by 34 publications

References 129 publications

Genome-wide association study of Buruli ulcer in rural Benin highlights role of two LncRNAs and the autophagy pathway

Genome-wide association study of Buruli ulcer in rural Benin highlights role of two LncRNAs and the autophagy pathway

Time-lapse 3D Imaging of Phagocytosis by Mouse Macrophages

Deoxypodophyllotoxin, a Lignan from Anthriscus sylvestris, Induces Apoptosis and Cell Cycle Arrest by Inhibiting the EGFR Signaling Pathways in Esophageal Squamous Cell Carcinoma Cells

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