Oral melatonin administration and programmed cell death of neutrophils, lymphocytes, and other cell types from rats injected with HL-60 cells

Programmed cell death occurs as a physiological process during development. In the brain and spinal cord this event determines the number and location of the different cell types. In adulthood, programmed cell death or apoptosis is more restricted but it may play a major role in different acute and chronic pathological entities. However, in contrast to other tissues where apoptosis has been widely documented from a morphological point of view, in the central nervous system complete anatomical evidence of apoptosis is scanty. In spite of this there is consensus about the activation of different signal systems associated to programmed cell death. In the present article we attempt to summarize the main apoptotic pathways so far identified in nervous tissue. Considering that apoptotic pathways are multiple, the neuronal cell types are highly diverse and specialized and that neuronal response to injury and survival depends upon tissue context, (i.e., preservation of connectivity, glial integrity and cell matrix, blood supply and trophic factors availability) what is relevant for the apoptotic process in a sector of the brain may not be important in another.

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Hormonal control of programmed cell death/apoptosis

Acta Endocrinologica ◽

10.1530/eje.0.1380482 ◽

1998 ◽

pp. 482-491 ◽

Cited By ~ 75

Author(s):

W Kiess ◽

B Gallaher

Keyword(s):

Cell Death ◽

Mammary Gland ◽

Growth Factors ◽

Growth Factor ◽

Programmed Cell Death ◽

Cell Types ◽

Hormonal Control ◽

Endocrine Glands ◽

Survival Factors ◽

Endocrine Tissues

Apoptosis or programmed cell death is a physiological form of cell death that occurs in embryonic development and during involution of organs. It is characterized by distinct biochemical and morphological changes such as DNA fragmentation, plasma membrane blebbing and cell volume shrinkage. Many hormones, cytokines and growth factors are known to act as general and/or tissue-specific survival factors preventing the onset of apoptosis. In addition, many hormones and growth factors are also capable of inducing or facilitating programmed cell death under physiological or pathological conditions, or both. Steroid hormones are potent regulators of apoptosis in steroid-dependent cell types and tissues such as the mammary gland, the prostate, the ovary and the testis. Growth factors such as epidermal growth factor, nerve growth factor, platelet-derived growth factor (PDGF) and insulin-like growth factor-I act as survival factors and inhibit apoptosis in a number of cell types such as haematopoietic cells, preovulatory follicles, the mammary gland, phaeochromocytoma cells and neurones. Conversely, apoptosis modulates the functioning and the functional integrity of many endocrine glands and of many cells that are capable of synthesizing and secreting hormones. In addition, exaggeration of the primarily natural process of apoptosis has a key role in the pathogenesis of diseases involving endocrine tissues. Most importantly, in autoimmune diseases such as autoimmune thyroid disease and type 1 diabetes mellitus, new data suggest that the immune system itself may not carry the final act of organ injury: rather, the target cells (i.e. thyrocytes and beta cells of the islets) commit suicide through apoptosis. The understanding of how hormones influence programmed cell death and, conversely, of how apoptosis affects endocrine glands, is central to further design strategies to prevent and treat diseases that affect endocrine tissues. This short review summarizes the available evidence showing where and how hormones control apoptosis and where and how programmed cell death exerts modulating effects upon hormonally active tissues.

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Role of Ced-3/ICE-family proteases in staurosporine-induced programmed cell death.

The Journal of Cell Biology ◽

10.1083/jcb.133.5.1041 ◽

1996 ◽

Vol 133 (5) ◽

pp. 1041-1051 ◽

Cited By ~ 270

Author(s):

M D Jacobsen ◽

M Weil ◽

M C Raff

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Mammalian Cell ◽

Mammalian Cells ◽

Apoptotic Cell ◽

Interleukin 1 ◽

Cell Types ◽

Cysteine Proteases ◽

A Cell ◽

Bona Fide

In the accompanying paper by Weil et al. (1996) we show that staurosporine (STS), in the presence of cycloheximide (CHX) to inhibit protein synthesis, induces apoptotic cell death in a large variety of nucleated mammalian cell types, suggesting that all nucleated mammalian cells constitutively express all of the proteins required to undergo programmed cell death (PCD). The reliability of that conclusion depends on the evidence that STS-induced, and (STS + CHS)-induced, cell deaths are bona fide examples of PCD. There is rapidly accumulating evidence that some members of the Ced-3/Interleukin-1 beta converting enzyme (ICE) family of cysteine proteases are part of the basic machinery of PCD. Here we show that Z-Val-Ala-Asp-fluoromethylketone (zVAD-fmk), a cell-permeable, irreversible, tripeptide inhibitor of some of these proteases, suppresses STS-induced and (STS + CHX)-induced cell death in a wide variety of mammalian cell types, including anucleate cytoplasts, providing strong evidence that these are all bona fide examples of PCD. We show that the Ced-3/ICE family member CPP32 becomes activated in STS-induced PCD, and that Bcl-2 inhibits this activation. Most important, we show that, in some cells at least, one or more CPP32-family members, but not ICE itself, is required for STS-induced PCD. Finally, we show that zVAD-fmk suppresses PCD in the interdigital webs in developing mouse paws and blocks the removal of web tissue during digit development, suggesting that this inhibition will be a useful tool for investigating the roles of PCD in various developmental processes.

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Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl.

Journal of Experimental Medicine ◽

10.1084/jem.182.5.1545 ◽

1995 ◽

Vol 182 (5) ◽

pp. 1545-1556 ◽

Cited By ~ 1934

Author(s):

S J Martin ◽

C P Reutelingsperger ◽

A J McGahon ◽

J A Rader ◽

R C van Schie ◽

...

Keyword(s):

Cell Death ◽

Plasma Membrane ◽

Programmed Cell Death ◽

General Feature ◽

Annexin V ◽

Cell Types ◽

Morphological Features ◽

Critical Event ◽

Specific Probe ◽

Macromolecular Synthesis

A critical event during programmed cell death (PCD) appears to be the acquisition of plasma membrane (PM) changes that allows phagocytes to recognize and engulf these cells before they rupture. The majority of PCD seen in higher organisms exhibits strikingly similar morphological features, and this form of PCD has been termed apoptosis. The nature of the PM changes that occur on apoptotic cells remains poorly defined. In this study, we have used a phosphatidylserine (PS)-binding protein (annexin V) as a specific probe to detect redistribution of this phospholipid, which is normally confined to the inner PM leaflet, during apoptosis. Here we show that PS externalization is an early and widespread event during apoptosis of a variety of murine and human cell types, regardless of the initiating stimulus, and precedes several other events normally associated with this mode of cell death. We also report that, under conditions in which the morphological features of apoptosis were prevented (macromolecular synthesis inhibition, overexpression of Bcl-2 or Abl), the appearance of PS on the external leaflet of the PM was similarly prevented. These data are compatible with the notion that activation of an inside-outside PS translocase is an early and widespread event during apoptosis.

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Apoptosis in lung injury and remodeling

Journal of Applied Physiology ◽

10.1152/japplphysiol.00519.2004 ◽

2004 ◽

Vol 97 (4) ◽

pp. 1535-1542 ◽

Cited By ~ 74

Author(s):

Xiaopeng Li ◽

Ruijie Shu ◽

Gerasimos Filippatos ◽

Bruce D. Uhal

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Cell Types ◽

Chronic Obstructive ◽

Disease Pathogenesis ◽

Obstructive Pulmonary Disease ◽

Recent Interest ◽

Timing Data ◽

Key Factor ◽

Culture Models

The mode of cell death termed apoptosis, sometimes referred to as programmed cell death, is as critical a determinant of cell population size as is cell proliferation. Although best characterized in cells of the immune system, apoptosis is now known to be a key factor in the maintenance of normal cell turnover within structural cells in the parenchyma of virtually every organ. Recent interest in apoptosis in the lung has sparked a surge of investigations designed to determine the roles of apoptosis in lung development, injury, and remodeling. Of particular recent interest are the roles of apoptosis in disease pathogenesis and resolution, in which the concept of apoptosis as a “programmed” cell death, i.e., genetically determined, is often more accurately viewed as “inappropriate cell suicide” with regard to its extent and/or timing. Data accumulating over the past decade have made clear the complexity of the control of lung cell apoptosis; concepts of the regulation of apoptosis originally determined in classical cell culture models are often, but not always, applicable to structural cells. For this reason, each of the many cell types of the lung must be studied as a potentially new subject with its own idiosyncrasies yet to be discovered. In light of the large volume of literature now available, this article focuses on the roles of apoptosis in three pathophysiological contexts: acute respiratory distress syndrome, chronic obstructive pulmonary disease, and pulmonary fibrosis. Each section presents key data describing the evidence for apoptosis in the lung, its possible relevance to disease pathogenesis, and proposed mechanisms that might suggest potential avenues for therapeutic intervention.

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Evaluation of Metaxylem Vessel Histogenesis and the Occurrence of Vessel Collapse during Early Development in Primary Roots of Zea mays ssp. mexicana: A Result of Premature Programmed Cell Death?

Plants ◽

10.3390/plants9030374 ◽

2020 ◽

Vol 9 (3) ◽

pp. 374

Author(s):

Susumu Saito ◽

Teruo Niki ◽

Daniel K. Gladish

Keyword(s):

Cell Death ◽

Zea Mays ◽

Programmed Cell Death ◽

Primary Root ◽

Cell Types ◽

Root Apical Meristem ◽

Root Tips ◽

Primary Roots ◽

Transmission Electron ◽

Vessel Elements

Root apical meristem histological organization in Zea mays has been carefully studied previously. Classical histology describes its system as having a “closed organization” and a development of xylem that conforms to predictable rules. Among the first cell types to begin differentiation are late-maturing metaxylem (LMX) vessels. As part of a larger study comparing domestic maize root development to a wild subspecies of Z. mays (teosinte), we encountered a metaxylem development abnormality in a small percentage of our specimens that begged further study, as it interrupted normal maturation of LMX. Primary root tips of young seedlings of Zea mays ssp. mexicana were fixed, embedded in appropriate resins, and sectioned for light and transmission electron microscopy. Longitudinal and serial transverse sections were analyzed using computer imaging to determine the position and timing of key xylem developmental events. We observed a severe abnormality of LMX development among 3.5% of the 227 mexicana seedlings we screened. All LMX vessel elements in these abnormal roots collapsed and probably became non-functional shortly after differentiation began. Cytoplasm and nucleoplasm in the abnormal LMX elements became condensed and subdivided into irregularly-shaped “macrovesicles” as their cell walls collapsed inward. We propose that these seedlings possibly suffered from a mutation that affected the timing of the programmed cell death (PCD) that is required to produce functional xylem vessels, such that autolysis of the cytoplasm was prematurely executed, i.e., prior to the development and lignification of secondary walls.

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Coordinate developmental regulation of purine catabolic enzyme expression in gastrointestinal and postimplantation reproductive tracts.

The Journal of Cell Biology ◽

10.1083/jcb.115.1.179 ◽

1991 ◽

Vol 115 (1) ◽

pp. 179-190 ◽

Cited By ~ 58

Author(s):

D P Witte ◽

D A Wiginton ◽

J J Hutton ◽

B J Aronow

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Embryo Implantation ◽

Cell Types ◽

Gi Tract ◽

Purine Nucleotides ◽

Postnatal Maturation ◽

Biochemical Adaptation ◽

Decidual Cells

Using histochemical detection, we have visualized in situ the complete metabolic pathway for the degradation of purine nucleotides. From the tongue to the ileum, diverse epithelial cell types lining the lumen of the mouse gastrointestinal (GI) tract strongly coexpress each of the five key purine catabolic enzymes. Dramatic increases in the expression of each enzyme occurred during postnatal maturation of the GI tract. Using in situ hybridization, an intense accumulation of adenosine deaminase (ADA) mRNA was detected only within GI epithelial cells undergoing postmitotic differentiation. In a similar manner, at the developing maternal-fetal interface, high level expression of the purine catabolic pathway also occurred in a unique subset of maternal decidual cells previously known to express high levels of alkaline phosphatase and ADA. This induction occurred almost immediately after implantation in the periembryonic maternal decidual cells, shortly thereafter in antimesometrial decidual cells, and later in cells of the placental decidua basalis: all of which contain cell types thought to be undergoing programmed cell death. The expression of the pathway at the site of embryo implantation appears to be critical because its pharmacologic inhibition during pregnancy has been found to be embryolethal or teratogenic. Purine destruction at these nutritional interfaces (placenta and gastrointestinal tract) seem to override any potential economy of purine salvage, and may represent biochemical adaptation to nucleic acid breakdown occurring in the context of dietary digestion or extensive programmed cell death.

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Vacuolar processing enzymes, AmVPE1 and AmVPE2, as potential executors of ethylene regulated programmed cell death in the lace plant (Aponogeton madagascariensis)

Botany ◽

10.1139/cjb-2017-0184 ◽

2018 ◽

Vol 96 (4) ◽

pp. 235-247 ◽

Cited By ~ 4

Author(s):

Gaolathe Rantong ◽

Arunika H.L.A.N. Gunawardena

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Leaf Development ◽

Cell Types ◽

Ethylene Biosynthesis ◽

Activity Levels ◽

Developmentally Regulated ◽

Transcript Levels ◽

Processing Enzymes ◽

Laser Capture Microscopy

Perforation formation in Aponogeton madagascariensis (Mirb.) H.Bruggen (lace plant) is an excellent model for studying developmentally regulated programmed cell death (PCD). In this study, we isolated and identified two lace plant vacuolar processing enzymes (VPEs) and investigated their involvement in PCD and throughout leaf development. Lace plant VPE transcript levels were determined during seven different stages of leaf development. PCD and non-PCD cells from “window” stage leaves (in which perforations are forming) were separated through laser-capture microscopy and their transcript levels were also determined. VPE activity was also studied between the cell types, through a VPE activity-based probe JOPD1. Additionally, VPE transcript levels were studied in plants treated with an ethylene biosynthesis inhibitor, aminoethoxyvinylglycine (AVG). The two isolated VPEs, AmVPE1 and AmVPE2, are vegetative type VPEs. AmVPE1 had higher transcript levels during a pre-perforation developmental stage, immediately prior to visible signs of PCD. AmVPE2 transcript levels were higher later during window and late window stages. Both VPEs had higher transcript and activity levels in PCD compared with the non-PCD cells. AVG treatment inhibited PCD and associated increases in VPE transcript levels. Our results suggested that VPEs are involved in the execution of the ethylene-related PCD in the lace plant.

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Anti-apogens and anti-engulfens: monoclonal antibodies reveal specific antigens on apoptotic and engulfment cells during chicken embryonic development

Development ◽

10.1242/dev.120.6.1421 ◽

1994 ◽

Vol 120 (6) ◽

pp. 1421-1431 ◽

Cited By ~ 2

Author(s):

R.J. Rotello ◽

P.A. Fernandez ◽

J. Yuan

Keyword(s):

Cell Death ◽

Monoclonal Antibodies ◽

Programmed Cell Death ◽

Apoptotic Cell ◽

Cell Types ◽

Apoptotic Cells ◽

Specific Antigens ◽

Common Leukocyte Antigen ◽

Cell Death Mechanisms ◽

Dying Cells

We have isolated a group of monoclonal antibodies that specifically recognize either apoptotic or engulfment cells in the interdigit areas of chicken hind limb foot plates, and throughout the embryo. Ten of these antibodies (anti-apogens) detect epitopes on dying cells that colocalize to areas of programmed cell death, characterized by the presence of apoptotic cells and bodies with typical cellular and nuclear morphology. Our results indicate that cells destined to die, or that are in the process of dying, express specific antigens that are not detectable in or on the surface of living cells. The detection of these apoptotic cell antigens in other areas of programmed cell death throughout the chick embryo indicates that different cell types, which form specific tissues and organs, may utilize similar cell death mechanisms. Six of the monoclonal antibodies (antiengulfens) define a class of engulfment cells which contain various numbers of apoptotic cells and/or apoptotic bodies in areas of programmed cell death. The immunostaining pattern of the anti-engulfen R15F is similar to that of an antibody against a common leukocyte antigen, suggesting the participation of cells from the immune system in the removal of apoptotic cell debris. These novel monoclonal antibody markers for apoptotic and engulfment cells will provide new tools to assist the further understanding of developmental programmed cell death in vertebrates.

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Programmed cell death by default in embryonic cells, fibroblasts, and cancer cells.

Molecular Biology of the Cell ◽

10.1091/mbc.6.11.1443 ◽

1995 ◽

Vol 6 (11) ◽

pp. 1443-1458 ◽

Cited By ~ 86

Author(s):

Y Ishizaki ◽

L Cheng ◽

A W Mudge ◽

M C Raff

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Cancer Cells ◽

Cell Line ◽

Mammalian Cells ◽

Cell Types ◽

Mouse Embryos ◽

Leukemia Cell Line ◽

Null Mouse ◽

Human Leukemia

We recently proposed that most mammalian cells constitutively express all of the proteins required to undergo programmed cell death (PCD) and undergo PCD unless continuously signaled by other cells not to. Although some cells have been shown to work this way, the vast majority of cell types remain to be tested. Here we tested purified fibroblasts isolated from developing or adult rat sciatic nerve, a mixture of cell types isolated from normal or p53-null mouse embryos, an immortalized rat fibroblast cell line, and a number of cancer cell lines. We found the following: 1) All of these cells undergo PCD when cultured at low cell density in the absence of serum and exogenous signaling molecules but can be rescued by serum or specific growth factors, suggesting that they need extracellular signals to avoid PCD. (2) The mixed cell types dissociated from normal mouse embryos can only support one another's survival in culture if they are in aggregates, suggesting that cell survival in embryos may depend on short-range signals. (3) Some cancer cells secrete factors that support their own survival. (4) The survival requirements of a human leukemia cell line change when the cells differentiate. (5) All of the cells studied can undergo PCD in the presence of cycloheximide, suggesting that they constitutively express all of the protein components required to execute the death program.

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