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Concept: Anoikis

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Whether responses of cells to extracellular environments affect the induction of apoptotic cell death is poorly understood. The current study aimed to unravel the different effects of culture media employed in vitro as extracellular environments on the susceptibility of cells to apoptosis. We found that apoptosis is stimulated to the higher levels by culturing human HeLa cells in Opti-MEM with unknown components, a medium that is specifically used for transfections, than by culturing cells in Dulbecco’s modified Eagle’s medium, a medium that is generally used for maintenance of cells. We showed that apoptosis is suppressed partially by culturing cells in heat-treated Opti-MEM, implicating a heat-sensitive component(s) in stimulating the apoptotic response of cells. Thus, different extracellular environments may contribute to different responses of cells to apoptosis, and this should be considered to evaluate the incidences of apoptotic cell death and could be applied to develop an efficient treatment for curing diseases such as cancer.

Concepts: Cancer, Death, Apoptosis, Cell culture, Programmed cell death, Vesicle, Caspase, Anoikis

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Contrast medium (CM) is widely used in cardiac catheterization; however, it may induce acute kidney injury or renal failure, although the underlying mechanism remains to be elucidated. MicroRNA‑21 (miR‑21) is involved in renal disease and has been indicated to regulate cellular apoptosis and fibrosis, although its role in CM‑induced renal cell injury is unknown. The present study examined the expression and potential targets of miR‑21 in human renal proximal tubular epithelial (HK‑2) cells following CM treatment. CM induced renal cell apoptosis and decreased miR‑21 expression. The expression level of the apoptosis regulator protein, B‑cell lymphoma 2 (Bcl‑2) was upregulated, whereas that of the apoptosis regulator, Bcl‑2‑associated X protein (Bax) was downregulated upon transfection of miR‑21 mimics; miR‑21 overexpression additionally directly inhibited the expression of programmed cell death protein 4 (PDCD4), as determined by a dual luciferase reporter assay, and PDCD4 silencing reduced the rate of HK‑2 cell apoptosis. The results of the present study indicated that miR‑21 protected renal cells against CM‑induced apoptosis by regulating PDCD4 expression.

Concepts: DNA, Renal failure, Kidney, Gene expression, Apoptosis, Programmed cell death, Caspase, Anoikis

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Cartilage injury induced by acute excessive contact stress is common and mostly affects young adult. Although early detection of cartilage injury may prevent serious and lifelong arthritic complications, early detection and treatment is not possible due to the lack of a reliable detection method. Since chondrocyte injury and subsequent cell death are the early signs of cartilage injury, it is likely that cartilage cell apoptosis can be used to predict the extent of injury. To test this hypothesis, a near infrared probe was fabricated to have high affinity to apoptotic cells. In vitro tests show that this apoptosis probe has low toxicity, high specificity, and high affinity to apoptotic cells. In addition, there is a positive relationship between apoptotic cell numbers and fluorescence intensities. Using a mouse xiphoid injury model, we found significant accumulation of the apoptosis probes at the injured xiphoid cartilage site. There was also a positive correlation between probe accumulation and the number of apoptotic chondrocytes within the injured xiphoid cartilage, which was confirmed by TUNEL assay. The results support that the apoptosis probes may serve as a powerful tool to monitor the extent of mechanical force-induced cartilage injury in vivo.

Concepts: Apoptosis, Cartilage, In vitro, Programmed cell death, Vesicle, Caspase, Chondrocyte, Anoikis

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Far from being passive, apoptotic cells influence their environment. For instance, they promote tissue folding, myoblast fusion and modulate tumor growth. Understanding the role of apoptotic cells necessitates their efficient tracking within living tissues, a task which is currently challenging. In order to easily spot apoptotic cells in developing Drosophila tissues, we generated a series of fly lines expressing different fluorescent sensors of caspase activity. We show that three of these reporters (GFP, Cerulean and Venus derived molecules) are detected specifically in apoptotic cells and throughout the whole process of programmed cell death. These reporters allow the specific visualization of apoptotic cells directly within living tissues, without any post-acquisition processing. They overcome the limitations of other apoptosis detection methods developed so far and notably, they can be combined with any kind of fluorophore.

Concepts: Immune system, Cancer, Apoptosis, Programmed cell death, Vesicle, Caspase, Bcl-2, Anoikis

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Apoptosis is genetically programmed cell death, an irreversible process of cell senescence with characteristic features different from other cellular mechanisms of death such as necrosis. In the last years, apoptosis has been extensively studied in the scientific literature, because it has been established that apoptosis plays a crucial role following the time course of chronic degenerative diseases, such as cancer. Thus, several researchers have strugged to detect what chemical agents are able to inter fere with the apoptotic process. Thus, the purpose of this literature review is to assess if fluoride induces apoptosis in mammalian cells using in vivo and in vitro test systems. Certain mammalian cell types such as oral cells, blood and brain were exetensively investigated; the results showed that fluoride is able to induce apoptosis in both intrinsinc and extrinsic pathways. Moreover, other cells types have been poorly investigated such as bone, kidney and reproductive cells with conflicting results so far. Therefore, this area needs further investigation for the safety of human populations exposed to fluoride in a chronic way, as for example in developing countries.

Concepts: Death, Cell division, Apoptosis, DNA repair, In vivo, Programmed cell death, Caspase, Anoikis

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Synaptic activity increases the resistance of neurons to diverse apoptotic insults; however, the underlying mechanisms remain less well understood. Zinc promotes cell survival under varied conditions, but the role of synaptically released zinc in the activity-dependent anti-apoptotic effect is unknown. Using cultured hippocampal slices and primary neurons we show that a typical apoptosis inducer-staurosporine (STP) was able to cause concentration-dependent apoptotic cell death in brain slices; Enhanced synaptic activity by bicuculline (Bic)/4-Aminopyridine (AP) treatment effectively prevented neurons from STP-induced cell apoptosis, as indicated by increased cell survival and suppressed caspase-3 activity. Application of Ca-EDTA, a cell membrane-impermeable zinc chelator which can efficiently capture the synaptically released zinc, completely blocked the neuronal activity-dependent anti-apoptotic effect. Same results were also observed in cultured primary hippocampal neurons. Therefore, our results indicate that synaptic activity improves neuronal resistance to apoptosis via synaptically released zinc.

Concepts: Brain, Apoptosis, Membrane potential, Programmed cell death, Caspase, XIAP, Anoikis

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Hypoxia is known to induce pancreatic beta cell dysfunction and apoptosis. Changes in Programmed Cell Death Gene 4 (PDCD4) expression have previously been linked with beta cell neogenesis and function. Our aim was to investigate the effects of hypoxia on cell viability, PDCD4 expression and subcellular localisation.

Concepts: Gene, Cell, Apoptosis, Pancreas, Beta cell, Programmed cell death, Caspase, Anoikis

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NSCLC accounts for about 85% of all lung cancer cases. Absence of miR-103 has recently identified to be associated withmetastatic capacity of primary lung tumors. However, the exact role of miR-103 in NSCLC and the molecular mechanism is unclear. In the present study, we showed that miR-103 expression was reduced in NSCLC tissues and cells. miR-103 expression was negatively correlated with tumor size and stage. The overall survival was longer in patients with higher miR-103 level than in those with lower miR-103 expression. miR-103 inhibited cell proliferation in A549 cells, decreased tumor weight and volume and prolonged survival of tumor-implanted nude mice. miR-103 increased apoptotic cell death A549 cells. Furthermore, miR-103 decreased the invasion and migration ability in A549 cells, as evidenced by Transwell and Wound healing results. Downregualtion of miR-103 significantly reduced programmed cell death 10 (PDCD10) level. We found a significant decrease to the relative luciferase activity of the reporter gene in A549 cells co-transfected with miR-103 mimic and pGL3-PDCD10 WT 3'-UTR, but not pGL3-PDCD10 mut 3'-UTR. We showed that overexpression of PDCD10 significantly inhibited miR-103-induced inhibition of cell proliferation, increased of apoptosis and decrease of invasion and migration in A549 cells. Moreover, we found that PDCD10 expression was increased in NSCLC tissues and cells. PDCD10 expression was positively correlated with tumor size and stage. Overexpression of PDCD10 increased cell proliferation and inhibited apoptosis in A549 cells. The data demonstrated that dysregulation of miR-103/PDCD10 signal may be a novel therapeutic target for the treatment of NSCLC.

Concepts: Gene, Gene expression, Cancer, Lung cancer, Apoptosis, Programmed cell death, Caspase, Anoikis

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Apoptosis is a programmed cell death playing key roles in physiology and pathophysiology of multi cellular organisms. Its nuclear manifestation requires transmission of the death signals across the nuclear pore complexes (NPCs). In strategic sequential steps apoptotic factors disrupt NPCs structure, integrity and barrier ultimately leading to nuclear breakdown. The present review reflects on these steps.

Concepts: Cell nucleus, Organism, Apoptosis, Nuclear pore, Prokaryote, Programmed cell death, Caspase, Anoikis