Pseudoapoptosis

Pseudoapoptosis can be defined from multiple viewpoints, with an underlying premise of the differences in cellular processes and states relating to apoptosis. Pseudoapoptosis can be referred to as an apoptotic-like cellular state that can be readily reversed,[1] or as a process that induces rapid apoptosis through the introduction of drugs such as bleomycin.[2]

Pseudoapoptosis has been used to define a cellular state closely resembling the initial stages of apoptosis, but asserts a readily reversible state of which a cell can resume normal cellular function. Chemical and morphological changes a cell may undergo associated with pseudoapoptosis include blebbing, plasma membrane lipid asymmetry, cytoskeleton alterations, changes in mitochondrial function, and increased concentration of cytosolic calcium. Regardless of these cellular alterations, pseudoapoptotic cells reverse these changes to resume normal cellular process.[1]

Pseudoapoptosis has also been used in some instances when describing an accelerated, drug induced apoptotic pathway by bleomycin. Cell death occurs as it would in apoptosis, but certain apoptotic mechanisms are not utilized when in the presence of bleomycin.[3][4]

Bleomycin

Bleomycin (BLM) is a cytotoxic, anticancerous drug that catalyzes double-stranded breaks (DSB) and single-stranded breaks (SSB) along DNA molecules. BLM has four distinguishable molecular components that determine function, including a DNA-binding region, metal binding domain, linker region, and a carbohydrate moiety. The metal binding domain associates with metals such as iron, cobalt, and zinc, each provides the basis of selectivity towards interaction with specific regions of DNA for catalytic cleavage. It is believed that the catalytic activity of BLM is carried out by associating with DNA molecules in linker regions between nucleosomes. Specific nucleotide sequences within the minor groove of a DNA molecule are a primary target as a catalytic site.[2]

At appropriate dosages, BLM generates morphological changes resembling typical apoptotic events, such as membrane blebbing and altered mitochondrial functioning. Degradation of DNA is also induced without the presence or assistance of specific endonuclease or protease that are involved under classic apoptotic conditions, which defines the usage of this form of pseudoapoptosis.[4] The relative dose administered determines the extent to which DNA fragmentation occurs. In the presence of large BLM concentrations, pseudoapoptosis is observed as rapid DNA fragmentation occurs, resulting in cell death in the absence of typical apoptotic components such as specific endonucleases and proteases.[4] Experimental evidence has suggested that every BLM molecule induces an average of 8 to 10 DNA strand breaks. An average ratio of 6 single-stranded breaks are generated for every double-stranded break. These numbers are dependent upon the form of BLM taken into consideration as deglyco-bleomycin has been found to be 100 times less toxic than wild-type BLM. Other forms of BLM forming complexes with various metals has suggested other variability when inducing pseudoapoptosis.[3]

ATP-gated P2X7 receptors

Studies have shown to induce apoptotic-like cellular states through the activation of ATP-gated P2X7 receptors, but under certain conditions these changes are reversed and normal cellular functions continue. This process has also been used to define pseudoapoptosis.[5]

Antigen-presenting cells contain membrane bound P2X7 receptors which are involved in acute inflammatory responses. P2X purinergic receptors are ATP-gated ion channels that become activated in the presence of extracellular adenosine triphosphate (ATP). Prolonged exposure to extracellular ATP can generate or couple to a variety of cellular responses, including cell fusion, cell proliferation, release of pro-inflammatory cytokines, and bone formation.[5]

When pertaining to apoptosis, prolonged activation of P2X7 receptors can stimulate stress responses resulting in activated kinases responsible for inducing morphological and chemical changes, leading to apoptotic events and subsequent cellular death. Experimental deduction has shown when cells are briefly exposed to high extracellular ATP on the order of seconds to minutes, pseudoapoptotic events will occur. Apoptotic events such as membrane blebbing, phosphatidylserine flips (exposure to extracellular space), mitochondrial swelling, and microvesicle shedding are present, but cellular death does not occur. All of these events have proven to be fully reversible. Sustained activation for a longer period of time leads to further mitochondrial swelling, resulting in the release of cytochrome c, which initiates a cascade of apoptotic events leading to cellular death.[5]

  • Membrane blebbing can be attributed to two separate pathways.
    • Calcium independent
    • Calcium Dependent
      • Rapid and reversible. Associated with extracellular phosphatidylserine exposure, membrane blebbing, with no release of cytochrome c.

References

  1. ^ a b Annmarie Surprenant, et al. "Pseudoapoptosis Induced By Brief Activation Of ATP-Gated P2X7 Receptors." Journal of Biological Chemistry 280.40 (2005): 33968-33976
  2. ^ a b Vorobjev, Pavel, Olessia Tchaika, and Valentina Zarytova. "Efficient Cleavage Of DS DNA By Bleomycin Conjugated Via Hexaethylene Glycol Linker To Triplex-Forming Oligonucleotides." Nucleosides, Nucleotides & Nucleic Acids 23.6/7 (2004): 1047-1051.
  3. ^ a b L M Mir, et al. "The Ratio Of Single- To Double-Strand DNA Breaks And Their Absolute Values Determine Cell Death Pathway." British Journal of Cancer 84.9 (2001): 1272
  4. ^ a b c L M Mir, et al. "In Vivo Evolution Of Tumour Cells After The Generation Of Double-Strand DNA Breaks." British Journal of Cancer 88.11 (2003): 1763.
  5. ^ a b c Annmarie Surprenant, et al. "Pseudoapoptosis Induced By Brief Activation Of ATP-Gated P2X7 Receptors." Journal of Biological Chemistry 280.40 (2005): 33968-33976.
Algor mortis

Algor mortis (Latin: algor—coldness; mortis—of death), the second stage of death, is the change in body temperature post mortem, until the ambient temperature is matched. This is generally a steady decline, although if the ambient temperature is above the body temperature (such as in a hot desert), the change in temperature will be positive, as the (relatively) cooler body acclimates to the warmer environment. External factors can have a significant influence.

The term was first used by Dowler in 1849. The first published measurements of the intervals of temperature after death were done by Dr John Davey in 1839.

Dead on arrival

Dead on arrival (DOA), also dead in the field and brought in dead (BID), indicates that a patient was found to be already clinically dead upon the arrival of professional medical assistance, often in the form of first responders such as emergency medical technicians, paramedics, or police.

In some jurisdictions, first responders must consult verbally with a physician before officially pronouncing a patient deceased, but once cardiopulmonary resuscitation is initiated, it must be continued until a physician can pronounce the patient dead.

Death hoax

A death hoax is a deliberate or confused report of someone's death that turns out to be incorrect and murder rumors. In some cases it might be because the person has intentionally faked death.

Death messenger

Death messengers, in former times, were those who were dispatched to spread the news that an inhabitant of their city or village had died. They were to wear unadorned black and go door to door with the message, "You are asked to attend the funeral of the departed __________ at (time, date, and place)." This was all they were allowed to say, and were to move on to the next house immediately after uttering the announcement. This tradition persisted in some areas to as late as the mid-19th century.

Death pose

Dinosaur and bird fossils are frequently found in a characteristic posture consisting of head thrown back, tail extended, and mouth wide open. The cause of this posture—sometimes called a "death pose"—has been a matter of scientific debate. Traditional explanations ranged from strong ligaments in the animal's neck desiccating and contracting to draw the body into the pose, to water currents randomly arranging the remains in the position.Faux and Padian suggested in 2007 that the live animal was suffering opisthotonus during its death throes, and that the pose is not the result of any post-mortem process at all. They also reject the idea of water as responsible for randomly arranging the bodies in a "death pose", as different parts of the body and the limbs can be in different directions, which they found unlikely to be the result of moving water. They also found that the claim that drying out of ligaments would make the position does not seem believable either.

Alicia Cutler and colleagues from Brigham Young University in Provo, Utah, think it is related to water. In 2012, paleontologists Achim G. Reisdorf and Michael Wuttke published a study regarding death poses. According to the conclusions of this study, the so-called "opisthotonic posture" is not the result of a cerebral illness creating muscle spasms, and also not of a rapid burial. Rather, peri-mortem submersion resulted in buoyancy that enabled the Ligamentum elasticum to pull the head and tail back.

Death rattle

Terminal respiratory secretions (or simply terminal secretions), known colloquially as a death rattle, are sounds often produced by someone who is near death as a result of fluids such as saliva and bronchial secretions accumulating in the throat and upper chest. Those who are dying may lose their ability to swallow and may have increased production of bronchial secretions, resulting in such an accumulation. Usually, two or three days earlier, the symptoms of approaching death can be observed as saliva accumulates in the throat, making it very difficult to take even a spoonful of water. Related symptoms can include shortness of breath and rapid chest movement. While death rattle is a strong indication that someone is near death, it can also be produced by other problems that cause interference with the swallowing reflex, such as brain injuries.It is sometimes misinterpreted as the sound of the person choking to death, or alternatively, that they are gargling.

Dignified death

Dignified death is a somewhat elusive concept often related to suicide. One factor that has been cited as a core component of dignified death is maintaining a sense of control. Another view is that a truly dignified death is an extension of a dignified life. There is some concern that assisted suicide does not guarantee a dignified death, since some patients may experience complications such as nausea and vomiting. There is some concern that age discrimination denies the elderly a dignified death.

Fan death

Fan death is a well-known superstition in Korean culture, where it is thought that running an electric fan in a closed room with unopened or no windows will prove fatal. Despite no concrete evidence to support the concept, belief in fan death persists to this day in Korea, and also to a lesser extent in Japan.

Lazarus sign

The Lazarus sign or Lazarus reflex is a reflex movement in brain-dead or brainstem failure patients, which causes them to briefly raise their arms and drop them crossed on their chests (in a position similar to some Egyptian mummies). The phenomenon is named after the Biblical figure Lazarus of Bethany, whom Jesus Christ raised from the dead in the Gospel of John.

Maceration (bone)

Maceration is a bone preparation technique whereby a clean skeleton is obtained from a vertebrate carcass by leaving it to decompose inside a closed container at near-constant temperature. This may be done as part of a forensic investigation, as a recovered body is too badly decomposed for a meaningful autopsy, but with enough flesh or skin remaining as to obscure macroscopically visible evidence, such as cut-marks. In most cases, maceration is done on the carcass of an animal for educational purposes.

Megadeath

Megadeath (or megacorpse) is one million human deaths, usually caused by a nuclear explosion. The term was used by scientists and thinkers who strategized likely outcomes of all-out nuclear warfare.

Necronym

A necronym (from the Greek words νεκρός, nekros, "dead" and ὄνομα ónoma, "name") is a reference to, or name of, a person who has died. Many cultures have taboos and traditions associated with referring to such a person. These vary from the extreme of never again speaking the person's real name, often using some circumlocution instead, to the opposite extreme of commemorating it incessantly by naming other things or people after the deceased.

For instance, in some cultures it is common for a newborn child to receive the name (a necronym) of a relative who has recently died, while in others to reuse such a name would be considered extremely inappropriate or even forbidden. While this varies from culture to culture, the use of necronyms is quite common.

Necrophobia

Necrophobia is a specific phobia which is the irrational fear of dead things (e.g., corpses) as well as things associated with death (e.g., coffins, tombstones, funerals, cemeteries). With all types of emotions, obsession with death becomes evident in both fascination and objectification. In a cultural sense, necrophobia may also be used to mean a fear of the dead by a cultural group, e.g., a belief that the spirits of the dead will return to haunt the living.Symptoms include: shortness of breath, rapid breathing, irregular heartbeat, sweating, dry mouth and shaking, feeling sick and uneasy, psychological instability, and an altogether feeling of dread and trepidation. The sufferer may feel this phobia all the time. The sufferer may also experience this sensation when something triggers the fear, like a close encounter with a dead animal or the funeral of a loved one or friend. The fear may have developed when a person witnessed a death, or was forced to attend a funeral as a child. Some people experience this after viewing frightening media.The fear can manifest itself as a serious condition. Treatment options include medication and therapy.The word necrophobia is derived from the Greek nekros (νεκρός) for "corpse" and the Greek phobos (φόβος) for "fear".

Obituary

An obituary (obit for short) is a news article that reports the recent death of a person, typically along with an account of the person's life and information about the upcoming funeral. In large cities and larger newspapers, obituaries are written only for people considered significant. In local newspapers, an obituary may be published for any local resident upon death. A necrology is a register or list of records of the deaths of people related to a particular organization, group or field, which may only contain the sparsest details, or small obituaries. Historical necrologies can be important sources of information.

Two types of paid advertisements are related to obituaries. One, known as a death notice, omits most biographical details and may be a legally required public notice under some circumstances. The other type, a paid memorial advertisement, is usually written by family members or friends, perhaps with assistance from a funeral home. Both types of paid advertisements are usually run as classified advertisements.

Pallor mortis

Pallor mortis (Latin: pallor "paleness", mortis "of death"), the first stage of death, is an after-death paleness that occurs in those with light/white skin.

Post-mortem interval

Post-mortem interval (PMI) is the time that has elapsed since a person has died. If the time in question is not known, a number of medical/scientific techniques are used to determine it. This also can refer to the stage of decomposition of the body.

Promession

Promession is an idea of how to dispose human remains by way of freeze drying. The concept of promession was developed by Swedish biologist Susanne Wiigh-Mäsak, who derived the name from the Italian word for "promise" (promessa). She founded Promessa Organic AB in 1997 to commercially pursue her idea. The company was liquidated 2015 without being able to produce a functioning facility. The idea of promession is questioned and not a functional method according to critics.

Rigor mortis

Rigor mortis (Latin: rigor "stiffness", mortis "of death"), or postmortem rigidity, is the third stage of death. It is one of the recognizable signs of death, characterized by stiffening of the limbs of the corpse caused by chemical changes in the muscles postmortem. In humans, rigor mortis can occur as soon as four hours after death.

Skeletonization

Skeletonization refers to the final stage of decomposition, during which the last vestiges of the soft tissues of a corpse or carcass have decayed or dried to the point that the skeleton is exposed. By the end of the skeletonization process, all soft tissue will have been eliminated, leaving only disarticulated bones. In a temperate climate, it usually requires three weeks to several years for a body to completely decompose into a skeleton, depending on factors such as temperature, humidity, presence of insects, and submergence in a substrate such as water. In tropical climates, skeletonization can occur in weeks, while in tundra areas, skeletonization may take years or may never occur, if subzero temperatures persist. Natural embalming processes in peat bogs or salt deserts can delay the process indefinitely, sometimes resulting in natural mummification.The rate of skeletonization and the present condition of a corpse or carcass can be used to determine the time of death.After skeletonization, if scavenging animals do not destroy or remove the bones, acids in many fertile soils take about 20 years to completely dissolve the skeleton of mid- to large-size mammals, such as humans, leaving no trace of the organism. In neutral-pH soil or sand, the skeleton can persist for hundreds of years before it finally disintegrates. Alternately, especially in very fine, dry, salty, anoxic, or mildly alkaline soils, bones may undergo fossilization, converting into minerals that may persist indefinitely.

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