Dissecting the Inorganic Nanoparticle-Driven Interferences on Adhesome Dynamics

Inorganic nanoparticles have emerged as an attractive theranostic tool applied to different pathologies such as cancer. However, the increment in inorganic nanoparticle application in biomedicine has prompted the scientific community to assess their potential toxicities, often preventing them from entering clinical settings. Cytoskeleton network and the related adhesomes nest are present in most cellular processes such as proliferation, migration, and cell death. The nanoparticle treatment can interfere with the cytoskeleton and adhesome dynamics, thus inflicting cellular damage. Therefore, it is crucial dissecting the molecular mechanisms involved in nanoparticle cytotoxicity. This review will briefly address the main characteristics of different adhesion structures and focus on the most relevant effects of inorganic nanoparticles with biomedical potential on cellular adhesome dynamics. Besides, the review put into perspective the use of inorganic nanoparticles for cytoskeleton targeting or study as a versatile tool. The dissection of the molecular mechanisms involved in the nanoparticle-driven interference of adhesome dynamics will facilitate the future development of nanotheranostics targeting cytoskeleton and adhesomes to tackle several diseases, such as cancer.

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Yeast Cells Exposed to Exogenous Palmitoleic Acid Either Adapt to Stress and Survive or Commit to Regulated Liponecrosis and Die

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/3074769 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Karamat Mohammad ◽

Paméla Dakik ◽

Younes Medkour ◽

Mélissa McAuley ◽

Darya Mitrofanova ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Cell Death ◽

Lipid Metabolism ◽

Lipid Droplets ◽

Palmitoleic Acid ◽

Molecular Mechanisms ◽

Neutral Lipids ◽

Yeast Cells ◽

Cellular Processes ◽

Regulated Cell Death

A disturbed homeostasis of cellular lipids and the resulting lipotoxicity are considered to be key contributors to many human pathologies, including obesity, metabolic syndrome, type 2 diabetes, cardiovascular diseases, and cancer. The yeast Saccharomyces cerevisiae has been successfully used for uncovering molecular mechanisms through which impaired lipid metabolism causes lipotoxicity and elicits different forms of regulated cell death. Here, we discuss mechanisms of the “liponecrotic” mode of regulated cell death in S. cerevisiae. This mode of regulated cell death can be initiated in response to a brief treatment of yeast with exogenous palmitoleic acid. Such treatment prompts the incorporation of exogenously added palmitoleic acid into phospholipids and neutral lipids. This orchestrates a global remodeling of lipid metabolism and transfer in the endoplasmic reticulum, mitochondria, lipid droplets, and the plasma membrane. Certain features of such remodeling play essential roles either in committing yeast to liponecrosis or in executing this mode of regulated cell death. We also outline four processes through which yeast cells actively resist liponecrosis by adapting to the cellular stress imposed by palmitoleic acid and maintaining viability. These prosurvival cellular processes are confined in the endoplasmic reticulum, lipid droplets, peroxisomes, autophagosomes, vacuoles, and the cytosol.

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Apoptosis in health and disease

Oxford Textbook of Medicine ◽

10.1093/med/9780199204854.003.0406 ◽

2010 ◽

pp. 177-188

Author(s):

Andrew H. Wyllie ◽

Mark J. Arends

Keyword(s):

Cell Death ◽

Molecular Mechanisms ◽

Apoptotic Cell ◽

Cytotoxic T Cells ◽

Single Cells ◽

Critical Role ◽

Adult Life ◽

Early Embryo ◽

Cellular Processes ◽

Living Tissues

Apoptosis is the process by which single cells die in the midst of living tissues. It is responsible for most—perhaps all—of the cell-death events that occur during the formation of the early embryo and the sculpting and moulding of organs. Apoptotic cell death continues to play a critical role in the maintenance of cell numbers in those tissues in which cell turnover persists into adult life, such as the epithelium of the gastrointestinal tract, the bone marrow, and lymphoid system including both B- and T-cell lineages. Apoptosis is the usual mode of death in the targets of natural killer (NK) cells and cytotoxic T-cells, and in involution and atrophy induced by hormonal and other stimuli. It also appears in the reaction of many tissues to injury, including mild degrees of ischaemia, exposure to ionizing and ultraviolet radiation, or treatment with cancer chemotherapeutic drugs. Excessive or too little apoptosis play a significant part in the pathogenesis of autoimmunity, infectious disease, AIDS, stroke, myocardial disease, and cancer. When cancers regress, apoptosis is part of the mechanism involved. Here the cellular processes and molecular mechanisms of apoptosis are set out, together with a conspectus of its involvement in many diseases....

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vitreal cells and specialized phagocytes in the chick embryo retina: A TEM and SEM study

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100159205 ◽

1990 ◽

Vol 48 (3) ◽

pp. 330-331

Author(s):

M.A. Cuadros ◽

M.J. Martinez-Guerrero ◽

A. Rios

Keyword(s):

Cell Death ◽

Plasma Membrane ◽

Acid Phosphatase ◽

Chick Embryo ◽

Basement Membrane ◽

Sem Images ◽

Intimate Contact ◽

Cellular Processes ◽

Sem Study ◽

Free Cells

In the chick embryo retina (days 3-4 of incubation), coinciding with an increase in cell death, specialized phagocytes characterized by intense acid phosphatase activity have been described. In these preparations, all free cells in the vitreal humor (vitreal cells) were strongly labeled. Conventional TEM and SEM techniques were used to characterize them and attempt to determine their relationship with retinal phagocytes.Two types of vitreal cells were distinguished. The first are located at some distance from the basement membrane of the neuroepithelium, and are rounded, with numerous vacuoles and thin cytoplasmic prolongations. Images of exo- and or endocytosis were frequent; the cells showed a well-developed Golgi apparatus (Fig. 1) In SEM images, the cells was covered with short cellular processes (Fig. 3). Cells lying parallel to or alongside the basement membrane are elongated. The plasma membrane is frequently in intimate contact with the basement membrane. These cells have generally a large cytoplasmic expansion (Fig. 5).

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Nano-Curcumin Regulates p53 Phosphorylation and PAI-1 Expression during Bleomycin Induced Injury in Alveolar Basal Epithelial Cells

Current Bioactive Compounds ◽

10.2174/1573407214666180727093612 ◽

2020 ◽

Vol 16 (1) ◽

pp. 85-89

Author(s):

Mahesh M. Gouda ◽

Ashwini Prabhu ◽

Varsha Reddy S.V. ◽

Rafa Jahan ◽

Yashodhar P. Bhandary

Keyword(s):

Epithelial Cells ◽

Lung Injury ◽

Molecular Mechanisms ◽

A549 Cells ◽

Plasminogen Activator Inhibitor ◽

Underlying Mechanism ◽

Protective Role ◽

Alveolar Epithelial Cells ◽

Cellular Damage

Background: Bleomycin (BLM) is known to cause DNA damage in the Alveolar Epithelial Cells (AECs). It is reported that BLM is involved in the up-regulation of inflammatory molecules such as neutrophils, macrophages, chemokines and cytokines. The complex underlying mechanism for inflammation mediated progression of lung injury is still unclear. This investigation was designed to understand the molecular mechanisms associated with p53 mediated modulation of Plasminogen Activator Inhibitor-I (PAI-I) expression and its regulation by nano-curcumin formulation. Methods: A549 cells were treated with BLM to cause the cellular damage in vitro and commercially available nano-curcumin formulation was used as an intervention. Cytotoxic effect of nano-curcumin was analyzed using Methyl Thiazolyl Tetrazolium (MTT) assay. Protein expressions were analyzed using western blot to evaluate the p53 mediated changes in PAI-I expression. Results: Nano-curcumin showed cytotoxicity up to 88.5 % at a concentration of 20 μg/ml after 48 h of treatment. BLM exposure to the cells activated the phosphorylation of p53, which in turn increased PAII expression. Nano-curcumin treatment showed a protective role against phosphorylation of p53 and PAI-I expression, which in turn regulated the fibro-proliferative phase of injury induced by bleomycin. Conclusion: Nano-curcumin could be used as an effective intervention to regulate the severity of lung injury, apoptosis of AECs and fibro-proliferation during pulmonary injury.

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Progress in understanding the role of lncRNA in programmed cell death

Cell Death Discovery ◽

10.1038/s41420-021-00407-1 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Na Jiang ◽

Xiaoyu Zhang ◽

Xuejun Gu ◽

Xiaozhuang Li ◽

Lei Shang

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Molecular Mechanisms ◽

Membrane Receptors ◽

Gene Expressions ◽

Apoptosis Pathway ◽

Stem Cell Pluripotency ◽

Extrinsic Apoptosis ◽

Related Proteins ◽

Cycle Regulation

AbstractLong non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides but not translated into proteins. LncRNAs regulate gene expressions at multiple levels, such as chromatin, transcription, and post-transcription. Further, lncRNAs participate in various biological processes such as cell differentiation, cell cycle regulation, and maintenance of stem cell pluripotency. We have previously reported that lncRNAs are closely related to programmed cell death (PCD), which includes apoptosis, autophagy, necroptosis, and ferroptosis. Overexpression of lncRNA can suppress the extrinsic apoptosis pathway by downregulating of membrane receptors and protect tumor cells by inhibiting the expression of necroptosis-related proteins. Some lncRNAs can also act as competitive endogenous RNA to prevent oxidation, thereby inhibiting ferroptosis, while some are known to activate autophagy. The relationship between lncRNA and PCD has promising implications in clinical research, and reports have highlighted this relationship in various cancers such as non-small cell lung cancer and gastric cancer. This review systematically summarizes the advances in the understanding of the molecular mechanisms through which lncRNAs impact PCD.

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Role of Long Non-Coding RNA Polymorphisms in Cancer Chemotherapeutic Response

Journal of Personalized Medicine ◽

10.3390/jpm11060513 ◽

2021 ◽

Vol 11 (6) ◽

pp. 513

Author(s):

Zheng Zhang ◽

Meng Gu ◽

Zhongze Gu ◽

Yan-Ru Lou

Keyword(s):

Molecular Mechanisms ◽

Neurological Diseases ◽

Cellular Processes ◽

Dna And Rna ◽

Chemotherapeutic Response ◽

Non Coding Rna ◽

Response To Chemotherapy ◽

Personalized Oncology ◽

Long Non Coding Rna

Genetic polymorphisms are defined as the presence of two or more different alleles in the same locus, with a frequency higher than 1% in the population. Since the discovery of long non-coding RNAs (lncRNAs), which refer to a non-coding RNA with a length of more than 200 nucleotides, their biological roles have been increasingly revealed in recent years. They regulate many cellular processes, from pluripotency to cancer. Interestingly, abnormal expression or dysfunction of lncRNAs is closely related to the occurrence of human diseases, including cancer and degenerative neurological diseases. Particularly, their polymorphisms have been found to be associated with altered drug response and/or drug toxicity in cancer treatment. However, molecular mechanisms are not yet fully elucidated, which are expected to be discovered by detailed studies of RNA–protein, RNA–DNA, and RNA–lipid interactions. In conclusion, lncRNAs polymorphisms may become biomarkers for predicting the response to chemotherapy in cancer patients. Here we review and discuss how gene polymorphisms of lncRNAs affect cancer chemotherapeutic response. This knowledge may pave the way to personalized oncology treatments.

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PGC-1α mediates a metabolic host defense response in human airway epithelium during rhinovirus infections

Nature Communications ◽

10.1038/s41467-021-23925-z ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Aubrey N. Michi ◽

Bryan G. Yipp ◽

Antoine Dufour ◽

Fernando Lopes ◽

David Proud

Keyword(s):

Host Defense ◽

Barrier Function ◽

Bacterial Infections ◽

Molecular Mechanisms ◽

Cellular Damage ◽

Epithelial Barrier ◽

Airway Epithelial ◽

Barrier Dysfunction ◽

Epithelial Barrier Function ◽

Epithelial Damage

AbstractHuman rhinoviruses (HRV) are common cold viruses associated with exacerbations of lower airways diseases. Although viral induced epithelial damage mediates inflammation, the molecular mechanisms responsible for airway epithelial damage and dysfunction remain undefined. Using experimental HRV infection studies in highly differentiated human bronchial epithelial cells grown at air-liquid interface (ALI), we examine the links between viral host defense, cellular metabolism, and epithelial barrier function. We observe that early HRV-C15 infection induces a transitory barrier-protective metabolic state characterized by glycolysis that ultimately becomes exhausted as the infection progresses and leads to cellular damage. Pharmacological promotion of glycolysis induces ROS-dependent upregulation of the mitochondrial metabolic regulator, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), thereby restoring epithelial barrier function, improving viral defense, and attenuating disease pathology. Therefore, PGC-1α regulates a metabolic pathway essential to host defense that can be therapeutically targeted to rescue airway epithelial barrier dysfunction and potentially prevent severe respiratory complications or secondary bacterial infections.

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DEAD-box helicases modulate dicing body formation in Arabidopsis

Science Advances ◽

10.1126/sciadv.abc6266 ◽

2021 ◽

Vol 7 (18) ◽

pp. eabc6266

Author(s):

Qi Li ◽

Ningkun Liu ◽

Qing Liu ◽

Xingguo Zheng ◽

Lu Lu ◽

...

Keyword(s):

Molecular Mechanisms ◽

Turnip Mosaic Virus ◽

Liquid Droplets ◽

Phase Separations ◽

Body Formation ◽

Cellular Processes ◽

Dead Box ◽

Body Components ◽

Liquid Phase Separations ◽

Spatiotemporal Control

Eukaryotic cells contain numerous membraneless organelles that are made from liquid droplets of proteins and nucleic acids and that provide spatiotemporal control of various cellular processes. However, the molecular mechanisms underlying the formation and rapid stress-induced alterations of these organelles are relatively uncharacterized. Here, we investigated the roles of DEAD-box helicases in the formation and alteration of membraneless nuclear dicing bodies (D-bodies) in Arabidopsis thaliana. We uncovered that RNA helicase 6 (RH6), RH8, and RH12 are previously unidentified D-body components. These helicases interact with and promote the phase separation of SERRATE, a key component of D-bodies, and drive the formation of D-bodies through liquid-liquid phase separations (LLPSs). The accumulation of these helicases in the nuclei decreases upon Turnip mosaic virus infections, which couples with the decrease of D-bodies. Our results thus reveal the key roles of RH6, RH8, and RH12 in modulating D-body formation via LLPSs.

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A Concerted Action of UBA5 C-Terminal Unstructured Regions Is Important for Transfer of Activated UFM1 to UFC1

International Journal of Molecular Sciences ◽

10.3390/ijms22147390 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7390

Author(s):

Nicole Wesch ◽

Frank Löhr ◽

Natalia Rogova ◽

Volker Dötsch ◽

Vladimir V. Rogov

Keyword(s):

Cellular Localization ◽

Molecular Mechanisms ◽

Biochemical Characterization ◽

Effective Interaction ◽

Regulatory Region ◽

Titration Calorimetry ◽

Enzymatic Reactions ◽

Cellular Processes ◽

Mechanism Of Interaction

Ubiquitin fold modifier 1 (UFM1) is a member of the ubiquitin-like protein family. UFM1 undergoes a cascade of enzymatic reactions including activation by UBA5 (E1), transfer to UFC1 (E2) and selective conjugation to a number of target proteins via UFL1 (E3) enzymes. Despite the importance of ufmylation in a variety of cellular processes and its role in the pathogenicity of many human diseases, the molecular mechanisms of the ufmylation cascade remains unclear. In this study we focused on the biophysical and biochemical characterization of the interaction between UBA5 and UFC1. We explored the hypothesis that the unstructured C-terminal region of UBA5 serves as a regulatory region, controlling cellular localization of the elements of the ufmylation cascade and effective interaction between them. We found that the last 20 residues in UBA5 are pivotal for binding to UFC1 and can accelerate the transfer of UFM1 to UFC1. We solved the structure of a complex of UFC1 and a peptide spanning the last 20 residues of UBA5 by NMR spectroscopy. This structure in combination with additional NMR titration and isothermal titration calorimetry experiments revealed the mechanism of interaction and confirmed the importance of the C-terminal unstructured region in UBA5 for the ufmylation cascade.

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Zebrafish Models of Autosomal Recessive Ataxias

Cells ◽

10.3390/cells10040836 ◽

2021 ◽

Vol 10 (4) ◽

pp. 836

Author(s):

Ana Quelle-Regaldie ◽

Daniel Sobrido-Cameán ◽

Antón Barreiro-Iglesias ◽

María Jesús Sobrido ◽

Laura Sánchez

Keyword(s):

Animal Models ◽

Autosomal Recessive ◽

Molecular Mechanisms ◽

System Development ◽

Rapid Development ◽

Nervous System Development ◽

Central Nervous System Development ◽

Cellular Processes ◽

Recessive Disorders

Autosomal recessive ataxias are much less well studied than autosomal dominant ataxias and there are no clearly defined systems to classify them. Autosomal recessive ataxias, which are characterized by neuronal and multisystemic features, have significant overlapping symptoms with other complex multisystemic recessive disorders. The generation of animal models of neurodegenerative disorders increases our knowledge of their cellular and molecular mechanisms and helps in the search for new therapies. Among animal models, the zebrafish, which shares 70% of its genome with humans, offer the advantages of being small in size and demonstrating rapid development, making them optimal for high throughput drug and genetic screening. Furthermore, embryo and larval transparency allows to visualize cellular processes and central nervous system development in vivo. In this review, we discuss the contributions of zebrafish models to the study of autosomal recessive ataxias characteristic phenotypes, behavior, and gene function, in addition to commenting on possible treatments found in these models. Most of the zebrafish models generated to date recapitulate the main features of recessive ataxias.

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