scholarly journals Calcium Signaling Regulates Autophagy and Apoptosis

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2125
Author(s):  
Pramod Sukumaran ◽  
Viviane Nascimento Da Conceicao ◽  
Yuyang Sun ◽  
Naseem Ahamad ◽  
Luis R Saraiva ◽  
...  
Keyword(s):  
Cell Survival ◽  
Neuronal Development ◽  
Critical Role ◽  
Therapeutic Interventions ◽  
Cellular Functions ◽  
Excitable Cells ◽  
Modulate Function ◽  
Promote Cell Survival ◽  
Regulatory Aspect

Calcium (Ca2+) functions as a second messenger that is critical in regulating fundamental physiological functions such as cell growth/development, cell survival, neuronal development and/or the maintenance of cellular functions. The coordination among various proteins/pumps/Ca2+ channels and Ca2+ storage in various organelles is critical in maintaining cytosolic Ca2+ levels that provide the spatial resolution needed for cellular homeostasis. An important regulatory aspect of Ca2+ homeostasis is a store operated Ca2+ entry (SOCE) mechanism that is activated by the depletion of Ca2+ from internal ER stores and has gained much attention for influencing functions in both excitable and non-excitable cells. Ca2+ has been shown to regulate opposing functions such as autophagy, that promote cell survival; on the other hand, Ca2+ also regulates programmed cell death processes such as apoptosis. The functional significance of the TRP/Orai channels has been elaborately studied; however, information on how they can modulate opposing functions and modulate function in excitable and non-excitable cells is limited. Importantly, perturbations in SOCE have been implicated in a spectrum of pathological neurodegenerative conditions. The critical role of autophagy machinery in the pathogenesis of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, would presumably unveil avenues for plausible therapeutic interventions for these diseases. We thus review the role of SOCE-regulated Ca2+ signaling in modulating these diverse functions in stem cell, immune regulation and neuromodulation.

scholarly journals Critical role of the IgM Fc receptor in IgM homeostasis, B-cell survival, and humoral immune responses

2012 ◽  
Vol 109 (40) ◽  
pp. E2699-E2706 ◽  
Author(s):  
R. Ouchida ◽  
H. Mori ◽  
K. Hase ◽  
H. Takatsu ◽  
T. Kurosaki ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Cell Survival ◽  
Critical Role ◽  
Fc Receptor ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
B Cell Survival

scholarly journals A critical role of autocrine sonic hedgehog signaling in human CD138+ myeloma cell survival and drug resistance

Blood ◽  
2014 ◽  
Vol 124 (13) ◽  
pp. 2061-2071 ◽  
Author(s):  
Zhiqiang Liu ◽  
Jingda Xu ◽  
Jin He ◽  
Yuhuan Zheng ◽  
Haiyan Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Survival ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Critical Role ◽  
Myeloma Cell ◽  
Sonic Hedgehog Signaling ◽  
Key Points

Key Points CD138+ MM cells are a major source of SHH. Autocrine SHH enhances MM drug resistance.

scholarly journals Dengue activates mTORC2 signaling to counteract apoptosis and maximize viral replication

2020 ◽  
Author(s):  
Christoph C. Carter ◽  
Jean Paul Olivier ◽  
Alexis Kaushansky ◽  
Fred D. Mast ◽  
John D. Aitchison
Keyword(s):  
Viral Replication ◽  
Cell Survival ◽  
Structural Protein ◽  
Protein Protein Interaction ◽  
Mechanistic Target Of Rapamycin ◽  
Promote Cell Survival ◽  
Important Regulator ◽  
Infected Cells ◽  
Induced Apoptosis

ABSTRACTThe mechanistic target of rapamycin (mTOR) functions in at least two distinct complexes: mTORC1, which regulates cellular anabolic-catabolic homeostasis, and mTORC2, which is an important regulator of cell survival and cytoskeletal maintenance. mTORC1 has been implicated in the pathogenesis of flaviviruses including dengue, where it contributes to the establishment of a pro-viral autophagic state. In contrast, the role of mTORC2 in viral pathogenesis is unknown. In this study, we explore the consequences of a physical protein-protein interaction between dengue non-structural protein 5 (NS5) and host cell mTOR proteins during infection. Using shRNA to differentially target mTORC1 and mTORC2 complexes, we show that mTORC2 is required for optimal dengue replication. Furthermore, we show that mTORC2 is activated during viral replication, and that mTORC2 counteracts virus-induced apoptosis, promoting the survival of infected cells. This work reveals a novel mechanism by which the dengue flavivirus can promote cell survival to maximize viral replication.

scholarly journals Aberrant Oligodendrogenesis in Down Syndrome: Shift in Gliogenesis?

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1591 ◽  
Author(s):  
Laura Reiche ◽  
Patrick Küry ◽  
Peter Göttle
Keyword(s):  
Down Syndrome ◽  
White Matter ◽  
Cell Fate ◽  
Neuronal Development ◽  
Demyelinating Diseases ◽  
Therapeutic Interventions ◽  
Cell Lineages ◽  
Cns Malformations ◽  
Current Experience

Down syndrome (DS), or trisomy 21, is the most prevalent chromosomal anomaly accounting for cognitive impairment and intellectual disability (ID). Neuropathological changes of DS brains are characterized by a reduction in the number of neurons and oligodendrocytes, accompanied by hypomyelination and astrogliosis. Recent studies mainly focused on neuronal development in DS, but underestimated the role of glial cells as pathogenic players. Aberrant or impaired differentiation within the oligodendroglial lineage and altered white matter functionality are thought to contribute to central nervous system (CNS) malformations. Given that white matter, comprised of oligodendrocytes and their myelin sheaths, is vital for higher brain function, gathering knowledge about pathways and modulators challenging oligodendrogenesis and cell lineages within DS is essential. This review article discusses to what degree DS-related effects on oligodendroglial cells have been described and presents collected evidence regarding induced cell-fate switches, thereby resulting in an enhanced generation of astrocytes. Moreover, alterations in white matter formation observed in mouse and human post-mortem brains are described. Finally, the rationale for a better understanding of pathways and modulators responsible for the glial cell imbalance as a possible source for future therapeutic interventions is given based on current experience on pro-oligodendroglial treatment approaches developed for demyelinating diseases, such as multiple sclerosis.

scholarly journals The structure and global distribution of the endoplasmic reticulum network are actively regulated by lysosomes

2020 ◽  
Vol 6 (51) ◽  
pp. eabc7209
Author(s):  
Meng Lu ◽  
Francesca W. van Tartwijk ◽  
Julie Qiaojin Lin ◽  
Wilco Nijenhuis ◽  
Pierre Parutto ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Nutritional Status ◽  
Neuronal Development ◽  
Critical Role ◽  
Causal Link ◽  
Global Distribution ◽  
Growth Defects ◽  
Cellular Environment ◽  
Axonal Extension

The endoplasmic reticulum (ER) comprises morphologically and functionally distinct domains: sheets and interconnected tubules. These domains undergo dynamic reshaping in response to changes in the cellular environment. However, the mechanisms behind this rapid remodeling are largely unknown. Here, we report that ER remodeling is actively driven by lysosomes, following lysosome repositioning in response to changes in nutritional status: The anchorage of lysosomes to ER growth tips is critical for ER tubule elongation and connection. We validate this causal link via the chemo- and optogenetically driven repositioning of lysosomes, which leads to both a redistribution of the ER tubules and a change of its global morphology. Therefore, lysosomes sense metabolic change in the cell and regulate ER tubule distribution accordingly. Dysfunction in this mechanism during axonal extension may lead to axonal growth defects. Our results demonstrate a critical role of lysosome-regulated ER dynamics and reshaping in nutrient responses and neuronal development.

Akt Activation Regulates Macrophage Survival and Differentiation: Role of M-CSF and Endogenous ROS.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2208-2208
Author(s):  
Yijie Wang ◽  
Mandy M. Zeigler ◽  
Greg K. Lam ◽  
Melissa G. Hunter ◽  
Tim D. Eubank ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Survival ◽  
Kinase Inhibitors ◽  
Critical Role ◽  
Annexin V ◽  
Mononuclear Phagocytes ◽  
Ros Generation ◽  
Blood Monocytes ◽  
Human Alveolar Macrophage

Abstract Previous reports from our laboratory showed M-CSF promotes PI 3-kinase activation resulting in the production of reactive oxygen species (ROS) and PI 3-kinase inhibitors, and the antioxidants diphenyleneiodonium (DPI) and n-acetyl cysteine (NAC) suppressed M-CSF-stimulated Erk activation. In this study, we hypothesized that M-CSF-induced generation of ROS affected Akt1 activation and sought to define the role of Akt1 in monocyte/macrophage survival and differentiation. We found that the production of ROS following M-CSF-treatment was inhibited by the antioxidant DPI. The addition of either DPI or NAC to the monocytes in the presence of M-CSF resulted in decrease cell survival as measured by Annexin V/PI and DNA fragmentation. In the cells treated with the antioxidants, there was a reduction in pAKT protein levels compared to M-CSF alone treatment suggesting that ROS contributed to Akt activity and cell survival. Macrophages from p47phox −/− mice, lacking a key component of the NADPH oxidase complex required for ROS generation were examined for M-CSF-induced survival and Akt1 activation. Bone marrow macrophages from p47phox −/ − mice and wild type (WT) littermates were isolated and differentiated in RPMI-1640 medium in the presence of 20 ng/ml of M-CSF for 5 days. We observed a reduction in Akt1 phosphorylation, cellular survival and increase in apoptosis measured by Annexin V/PI staining in p47phox −/ − macrophages compared to WT controls. Since macrophages from the p47phox−/− mice had reduced Akt1 activity and cell survival to M-CSF stimulation, we next wanted to independently evaluate the role of Akt in macrophage survival and differentiation. We therefore examined macrophages from mice that had targeted expression of activated Akt1 (Myr-Akt1) in mononuclear phagocytes. Bone marrow from Myr-Akt1 mice and (WT) littermates was isolated and cultured in the presence of 20 ng/ml of M-CSF for 5 days. We found that Myr-Akt1 cells had enhanced survival and reduced apoptosis versus WT cells. Interestingly, Myr-Akt1 mice had normal circulating numbers of monocytes, but had splenomegaly and increased numbers of mature macrophages in their spleens by CD68 staining. Since the expression of Myr-Akt1 in BMM enhanced cell survival, we were interested in the effect in human monocytes. Peripheral blood monocytes (PBM) were transiently transfected with Myr-Akt1 constructs. We observed a decrease in Annexin V/PI staining indicating promotion of cell survival in PBM expressing Myr-Akt compared to untransfected PBM. Since Akt1 appeared to be important for macrophage survival/differentiation, we examined its contribution in human alveolar macrophage homeostasis and found that freshly isolated macrophages had constitutive Akt1 activity and had increased levels of Akt1 protein. This data support a critical role for Akt1 in macrophage differentiation in mice. Together, our findings may provide insight in the pathogenesis of monocyte/macrophage homeostasis.

scholarly journals Acupuncture May Exert Its Therapeutic Effect through MicroRNA-339/Sirt2/NFκB/FOXO1 Axis

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Jia-You Wang ◽  
Hui Li ◽  
Chun-Mei Ma ◽  
Jia-Lu Wang ◽  
Xin-Sheng Lai ◽  
...  
Keyword(s):  
Acupuncture Therapy ◽  
Critical Role ◽  
Luciferase Assay ◽  
Cellular Functions ◽  
Physiological Level ◽  
Forkhead Box ◽  
Bioinformatics Study ◽  
Direct Target ◽  
Future Work

Recently, we have found that a number of microRNAs (miRNAs) and proteins are involved in the response to acupuncture therapy in hypertensive rats. Our bioinformatics study suggests an association between these miRNAs and proteins, which include miR-339 and sirtuin 2 (Sirt2). In this paper, we aimed to investigate whether Sirt2 was a direct target of miR-339 in neurons. In human SH-SY5Y cells, the luciferase assay implied that Sirt2 was likely a target of miRNA-339. Overexpression of miR-339 downregulated Sirt2 expression, while knockdown of miR-339 upregulated Sirt2 expression in human SH-SY5Y cells and rat PC12 cells. In addition, overexpression of miR-399 increased the acetylation of nuclear factor-κB (NF-κB) and forkhead box protein O1 (FOXO1) in SH-SY5Y cells, which are known targets of Sirt2. Our findings demonstrate that miR-339 regulates Sirt2 in human and rat neurons. Since Sirt2 plays a critical role in multiple important cellular functions, our data imply that acupuncture may act through epigenetic changes and subsequent action on their targets, such as miRNA-339/Sirt2/NF-κB/FOXO1 axis. Some physiological level changes of neurons after altering the miR-339 levels are needed to validate the suggested therapeutic role of miR-339/Sirt2/NF-κB/FOXO1 axis in response to acupuncture therapy in the future work.

scholarly journals Chemokine-biased robust self-organizing polarization of migrating cells in vivo

2019 ◽  
Author(s):  
Adan Olguin-Olguin ◽  
Anne Aalto ◽  
Benoît Maugis ◽  
Michal Reichman-Fried ◽  
Erez Raz
Keyword(s):  
Primordial Germ Cells ◽  
Critical Role ◽  
Cell Polarization ◽  
Cellular Functions ◽  
Motile Cells ◽  
Cell Front ◽  
Specific Proteins ◽  
Migrating Cells

The mechanisms facilitating the establishment of front-rear polarity in migrating cells are not fully understood, in particular in the context of bleb-driven directional migration. To gain further insight into this issue we utilized the migration of zebrafish primordial germ cells (PGCs) as an in vivo model. We followed the molecular and morphological cascade that converts apolar cells into polarized bleb-forming motile cells and analyzed the cross dependency among the different cellular functions we identified. Our results underline the critical role of antagonistic interactions between the front and the rear, in particular the role of biophysical processes including formation of barriers and transport of specific proteins to the back of the cell. These interactions direct the formation of blebs to a specific part of the cell that is specified as the cell front. In this way, spontaneous cell polarization facilitates non-directional cell motility and when biased by chemokine signals leads to migration towards specific locations.

PtdIns5P: a little phosphoinositide with big functions?

2007 ◽  
Vol 74 ◽  
pp. 117-128 ◽  
Author(s):  
Sophie Coronas ◽  
Damien Ramel ◽  
Caroline Pendaries ◽  
Frédérique Gaits-Iacovoni ◽  
Hélène Tronchère ◽  
...  
Keyword(s):  
Potential Role ◽  
Current Knowledge ◽  
Critical Role ◽  
Cell Regulation ◽  
Cellular Functions ◽  
Minor Constituents ◽  
Signalling Molecules ◽  
Phosphoinositide 3 Kinase ◽  
Synthesis And Degradation

Phosphoinositides are minor constituents of cell membranes playing a critical role in the regulation of many cellular functions. Recent discoveries indicate that mutations in several phosphoinositide kinases and phosphatases generate imbalances in the levels of phosphoinositides, thereby leading to the development of human diseases. Although the roles of phosphoinositide 3-kinase products and PtdIns(4,5)P2 were largely studied these last years, the potential role of phosphatidylinositol monophosphates as direct signalling molecules is just emerging. PtdIns5P, the least characterized phosphoinositide, appears to be a new player in cell regulation. This review will summarize the current knowledge on the mechanisms of synthesis and degradation of PtdIns5P as well as its potential roles.

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