Cell Death and Organ Injury: The Example of the Kidney

Author(s):  
Giovanna Priante ◽  
Lisa Gianesello ◽  
Monica Ceol ◽  
Dorella Del Prete ◽  
Franca Anglani
Keyword(s):  
2018 ◽  
Vol 315 (5) ◽  
pp. G838-G847 ◽  
Author(s):  
Yu-pu Hong ◽  
Wen-hong Deng ◽  
Wen-yi Guo ◽  
Qiao Shi ◽  
Liang Zhao ◽  
...  

This study was conducted to investigate the effect of 4-phenylbutyric acid (4-PBA) on vital organ injury following sodium taurocholate-induced acute pancreatitis (AP) in rats and the pertinent mechanism. The serum biochemical indicators and key inflammatory cytokines, histopathological damage and apoptosis of vital organs in rat AP, were evaluated in the presence or absence of 4-PBA. Moreover, mRNA and protein levels of endoplasmic reticulum stress (ERS) markers were assessed. 4-PBA significantly attenuated the structural and functional damage of vital organs, including serum pancreatic enzymes, hepatic enzymes, creatinine, and urea. The morphological changes and infiltration of neutrophils and macrophages were reduced as well. These effects were accompanied by decreased serum levels of proinflammatory TNF-α and IL-1β. Furthermore, 4-PBA diminished the expression of ERS markers (glucose-regulated protein 78, CCAAT/enhancer-binding protein homologous protein, protein kinase R-like ER kinase, activated transcription factor 6, and type-1 inositol requiring enzyme) in vital organs of AP rats. 4-PBA also reduced AP-induced apoptosis in lung, liver, and kidney tissues as shown by TUNEL assay. The present study demonstrated that 4-PBA protected pancreas, lung, liver, and kidney from injury in rat AP by regulating ERS and mitigating inflammatory response to restrain cell death and further suggested that 4-PBA may have potential therapeutic implications in the disease. NEW & NOTEWORTHY In this study, we suggest that endoplasmic reticulum stress (ERS) is an important player in the development of acute pancreatitis-induced multiorgan injury, providing additional evidence for the proinflammatory role of ERS. Because 4-phenylbutyric acid has been suggested to inhibit ERS in many pathological conditions, it is possible that this effect can be involved in alleviating inflammatory response and cell death to ameliorate vital organ damage following acute pancreatitis induced by sodium taurocholate in rats.


Inflammation ◽  
2020 ◽  
Vol 43 (6) ◽  
pp. 2021-2032 ◽  
Author(s):  
Zhen Cahilog ◽  
Hailin Zhao ◽  
Lingzhi Wu ◽  
Azeem Alam ◽  
Shiori Eguchi ◽  
...  

Abstract NETosis is a type of regulated cell death dependent on the formation of neutrophil extracellular traps (NET), where net-like structures of decondensed chromatin and proteases are produced by polymorphonuclear (PMN) granulocytes. These structures immobilise pathogens and restrict them with antimicrobial molecules, thus preventing their spread. Whilst NETs possess a fundamental anti-microbial function within the innate immune system under physiological circumstances, increasing evidence also indicates that NETosis occurs in the pathogenic process of other disease type, including but not limited to atherosclerosis, airway inflammation, Alzheimer’s and stroke. Here, we reviewed the role of NETosis in the development of organ injury, including injury to the brain, lung, heart, kidney, musculoskeletal system, gut and reproductive system, whilst therapeutic agents in blocking injuries induced by NETosis in its primitive stages were also discussed. This review provides novel insights into the involvement of NETosis in different organ injuries, and whilst potential therapeutic measures targeting NETosis remain a largely unexplored area, these warrant further investigation.


Author(s):  
Anne F. Bushnell ◽  
Sarah Webster ◽  
Lynn S. Perlmutter

Apoptosis, or programmed cell death, is an important mechanism in development and in diverse disease states. The morphological characteristics of apoptosis were first identified using the electron microscope. Since then, DNA laddering on agarose gels was found to correlate well with apoptotic cell death in cultured cells of dissimilar origins. Recently numerous DNA nick end labeling methods have been developed in an attempt to visualize, at the light microscopic level, the apoptotic cells responsible for DNA laddering.The present studies were designed to compare various tissue processing techniques and staining methods to assess the occurrence of apoptosis in post mortem tissue from Alzheimer's diseased (AD) and control human brains by DNA nick end labeling methods. Three tissue preparation methods and two commercial DNA nick end labeling kits were evaluated: the Apoptag kit from Oncor and the Biotin-21 dUTP 3' end labeling kit from Clontech. The detection methods of the two kits differed in that the Oncor kit used digoxigenin dUTP and anti-digoxigenin-peroxidase and the Clontech used biotinylated dUTP and avidinperoxidase. Both used 3-3' diaminobenzidine (DAB) for final color development.


Author(s):  
S. Trachtenberg ◽  
P.M. Steinert ◽  
B.L. Trus ◽  
A.C. Steven

During terminal differentiation of vertebrate epidermis, certain specific keratin intermediate filament (KIF) proteins are produced. Keratinization of the epidermis involves cell death and disruption of the cytoplasm, leaving a network of KIF embedded in an amorphous matrix which forms the outer horny layer known as the stratum corneum. Eventually these cells are shed (desquamation). Normally, the processes of differentiation, keratinization, and desquamation are regulated in an orderly manner. In psoriasis, a chronic skin disease, a hyperkeratotic stratum corneum is produced, resulting in abnormal desquamation of unusually large scales. In this disease, the normal KIF proteins are diminished in amount or absent, and other proteins more typical of proliferative epidermal cells are present. There is also evidence of proteolytic degradation of the KIF.


Author(s):  
Eric Hallberg ◽  
Lina Hansén

The antennal rudiments in lepidopterous insects are present as disks during the larval stage. The tubular double-walled antennal disk is present beneath the larval antenna, and its inner layer gives rise to the adult antenna during the pupal stage. The sensilla develop from a cluster of cells that are derived from one stem cell, which gives rise to both sensory and enveloping cells. During the morphogenesis of the sensillum these cells undergo major transformations, including cell death. In the moth Agrotis segetum the pupal stage lasts about 14 days (temperature, 25°C). The antennae, clearly seen from the exterior, were dissected and fixed according to standard procedures (3 % glutaraldehyde in 0.15 M cacaodylate buffer, followed by 1 % osmiumtetroxide in the same buffer). Pupae from day 1 to day 8, of both sexes were studied.


Author(s):  
M.A. Cuadros ◽  
M.J. Martinez-Guerrero ◽  
A. Rios

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).


2020 ◽  
Vol 48 (2) ◽  
pp. 613-620
Author(s):  
Clara Ortegón Salas ◽  
Katharina Schneider ◽  
Christopher Horst Lillig ◽  
Manuela Gellert

Processing of and responding to various signals is an essential cellular function that influences survival, homeostasis, development, and cell death. Extra- or intracellular signals are perceived via specific receptors and transduced in a particular signalling pathway that results in a precise response. Reversible post-translational redox modifications of cysteinyl and methionyl residues have been characterised in countless signal transduction pathways. Due to the low reactivity of most sulfur-containing amino acid side chains with hydrogen peroxide, for instance, and also to ensure specificity, redox signalling requires catalysis, just like phosphorylation signalling requires kinases and phosphatases. While reducing enzymes of both cysteinyl- and methionyl-derivates have been characterised in great detail before, the discovery and characterisation of MICAL proteins evinced the first examples of specific oxidases in signal transduction. This article provides an overview of the functions of MICAL proteins in the redox regulation of cellular functions.


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