25 de Nov de 2019

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  1.  The number of cells in a body of organism is tightly regulated. Its not only the control over cell division but also on rate of cell death.  Controlled cell death is needed for normal development and good health throughout life along with normal development of cells and cell cycle maturation.
  2.  APOPTOSIS: Genetically programmed process of deliberate sucide by an unwanted cell in a multicellular organism.  AUTOPHAGY : Plays a housekeeping role in removing misfold proteins, clearing damaged organelles as well as eliminating intracellular pathogens.  NECROSIS : Non-programmed cell death, death of a cell caused by external factors such as trauma or infection.  NECROPTOSIS : Programmed form of necrosis.  ONCOSIS: Series of cellular reactions following injury that ultimately leads to cell death. CELL DEATH NECROSIS NECROPTOSIS ONCOSIS IMMUNOGENIC CELL DEATH AUTOPHAGY APOPSTOSIS
  3.  Often occurs when the structure they form is no longer needed.  To eliminate abnormal cells, cells that non-functional or potentially dangerous to the animal.  Cell death can prevent viral replication because they need a cell alive to reproduce.  Failure of cells to die or cells dying when they shouldn’t can lead to many diseases.
  4.  Cell death occur in many ways. 1.Infection 2.Poisioning 3.Lack of oxygen  An uncontrolled death messy. In this cells swells up and its contents leak away. This may damae surrounding cells too.  On the other hand, there is another tidier way to go, i.e., Programmed cell death or apopstosis, in which cell often choose to kill themselves.
  5.  During viral infections.  During DNA damage.  To make way for new cells.  Ex: In the womb, our fingers and toes are connected to one another by a sort of webbing. Apopstosis is what causes that webbing to disappear, leaving us with 10 separate digits.  As our brains develop, the body creates millions more cells than it needs, the ones that don’t form synaptic connections undergo apopstosis so that remaining cells function well.  Programmed cell death is also necessary to prevent from efeect of spurious infection in plants.
  6.  During viral infections.  During DNA damage.  To make way for new cells.  Ex: In the womb, our fingers and toes are connected to one another by a sort of webbing. Apopstosis is what causes that webbing to disappear, leaving us with 10 separate digits.  As our brains develop, the body creates millions more cells than it needs, the ones that don’t form synaptic connections undergo apopstosis so that remaining cells function well.  Programmed cell death is also necessary to prevent from efeect of spurious infection in plants.
  7.  Mediated by an intacellular program.  It includes mainly-Apopstosis and Autophagy.  Non-apoptopic programmed cell death - can function as either backup mechanisms or the main type of PCD.  It is not only confined to animals, in plants also it occurs during development and in the senescence of flowers and leaves.  PCD also occurs in unicellular organisms including yeasts and bacteria.
  8.  It is characterized by compact cytoplasm, vacuoles in the cytoplasm membrane, nuclear chromatin condensation, DNA fragmentation and the formation of apoptotic bodies.  At the periphery of the nuclear membrane, chromatin condensation starts, forming a ring like structure.  Later on, the nucleus progressively condenses and breaks up (karyorrhexis).  The cell detaches from the surrounding tissue and its outlines become convoluted and form extensions.  The apoptotic bodies are rapidly phagocytosed into neighbouring cells, including macrophages and parenchymal cells. Apoptotic bodies can be recognised inside these cells, but eventually they become degraded.
  9.  Variety of stimuli.  Withdrawl of essential growth factors.  Gamma irradiation.  Treatment with glucocorticoids.  Activation of certain receptors.  In immune system, it is initiated where Tc lymphocytes attack target cell.
  10.  Apoptosis is a tightly regulated and efficient cell death program involving multiple factors.  Caspases take major and a central role in apoptotic mechanism. The term caspases is derived from cysteine-dependent aspartate-specific proteases. Caspases are central to the mechanism of apoptosis as they are both the initiators and executioners.  Contain key cysteine residue at catalytic site.  Cleave protein at site just C-terminal to aspartate residue. INITIATORS EFFECTOR/EXECUTIONERS CASPASES 2, 8, 9 and 10 CASPASES 3, 6 and 7
  12.  Cell activate their apoptopic programs from inside the cell in response to injury or other stresses like DNA damage or lack of oxygen, nutrients or free radicals, growth factors deprivation.  Mitochondria dependent pathway.  Regulated by BCl-2 family of proteins (B cell lymphoma-2 gene)  Approximately 15 members of Bcl-2 family present.  Human Bcl-2 protein can suppress apoptosis when expressed in C.elegans.
  13. BCl-2 family proteins Pro-apoptopic Promote apoptosis BH123 proteins (Bax, Bak) BH 3-only proteins (Bid, Bim, Bik, Bad, PUMA, NOXA) Anti-apoptopic Inhibit apoptosis (Bcl-2, Bcl-XL, Mcl-1, Bcl-1)
  14.  BH123 proteins become activate and induces release of Cyt c and other intermembrane proteins from mitochondria into the cytosol.  Bax, Bak- main BH123 proteins atleast 1 of them is required for the intrinsic pathway of apoptosis to operate.  Mutant mouse cells that lack both the proteins are resistant to all pro-apoptopic signal.  BH3 only proteins-promote apoptosis mainly by inhibiting anti-apoptopic Bcl2 proteins.
  15.  Apoptopic signals (cell stress, free radicle damage, etc.,)  Pro-apoptopic BH-3 proteins in the cytosol gets activated.  BH123 proteins relocate to the surface of mitochondria.  Interaction of pro and anti apoptopic proteins- disruption of anti apoptopic, Bcl2 proteins.  Leads to formation of PT (Permeability transition pore)  Activated BH123 proteins promote release of AIF (Apoptosis Inducing Factor), DIALBO & Cyt c into the cytosol.  Activation of Apaf 1 (Apoptotic protease activating factor-1).
  16. • Apaf 1 oligomerize into a wheel-like heptamer complex called Apoptosome. • Recruitment & activation of Procaspase 9 through CARD domain. • Activation of Caspase 3 • Execution pathway.
  17.  Extracellular signal proteins binds to cell surface death receptors that trigger the extrinsic pathway.  Death receptors are transmembrane proteins having extracellular ligand binding domain, transmembrane domain and an intracellular death domain which activated the apoptopic program.  Ligands and death receptors are homotrimers.  Receptor belongs to TNF (Tumor Necrosis Factor) receptor family. TNF receptor (binds to TNFα ligand) and Fas death receptor (binds to Fas ligand).
  18.  Fas ligand on cells binds to Fas receptor on target cell.  Death domains then recruits intracellular adaptor proteins-  FADD (Fas ligand associated death domain)  TRADD ( TNFα receptor associated death domain)  It then recruits pro caspase 8 or 10, forming DISC (Death Inducing Signalling Complex)  Activation or cleavage of procaspase 8 or 10.  Formation of Caspase 8 or 10  Caspase 3 activation  Execution pathway.
  19.  Another pathway of apoptosis.  It involves interaction between Cytotoxic T cells/ CD8+ and infected cell (viral / cancerous)  It is a type of Intrinsic pathway as. It involves cellular components. Doesn’t involve ligand receptor concept. Independent of Receptor mediated pathway.  Perforin is a pore forming protein and also known as cytoplasmic granule toxins.  Granzyme is a family of structurally related serine protease stored within the cytotoxic granules of cytotoxic lymphocytes.
  20.  Anti-cancer drugs and radiation work by triggering apoptosis in diseased cells.  If apoptosis is stopped, uncontrolled cell division happen leading to cancer.  Many diseases and disorders are linked with the life and death of the cells, increase apoptosis is a characteristic of AIDS, Alzhemer’s and Parkinson’s disease. While deceases apoptosis can signal cancer.  Autoimmune disease will occur.  Improper cell cycle.
  21.  It is commonly known that animal pathogens often target and suppress programmed cell death (PCD) pathway components to manipulate their hosts.  In contrast, plant pathogens often trigger PCD. In cases in which plant PCD accompanies disease resistance, an event called the hypersensitive response.  In plants without genetic disease resistance, these secreted molecules serve as virulence factors that act through largely unknown mechanisms. A number of fungal pathogens secrete PCD-promoting molecules that are critical virulence factor.  HR cell death is an active process in which the accumulation of 02 -and H202 leads to an elevation in cytosolic Ca2+ and triggers a protein kinase-mediated cell death process that is similar physiologically to PCD.
  22.  Perhaps the most well-known cell death response in plants is the hypersensitive response (HR) associated with a phenomenon termed the resistance response (RR).  The RR involves the co-ordinate activation of many defences that limit pathogen growth.  HR is considered to be only the cell death component of the RR.  An RR is triggered when the host has a dominant R gene that corresponds to a dominant avr gene in the pathogen. Pathogen AVR avr Host R- Incompatible (Resistant) Compatible (Susceptible) rr Compatible (Susceptible) Compatible (Susceptible)
  23.  The view that the HR is an active process of the host and may be a form of programmed cell death (PCD) was supported by early observations that host cells must be metabolically active and, in some cases, the HR requires active host protein synthesis for its induction by fungi and bacteria.  The morphology of cells undergoing the HR at late stages suggest that it is a form of PCD with some apoptotic features.  In particular, apoptotic like bodies with avirulent Pseudomonas syringae infections were observed (Levine et al., 1996).  It was found early changes in mitochondrial morphology (swelling and cristae disorganization) in avirulent P. syringae-infected lettuce, similar to what occurs in animal cells undergoing apoptosis (Wakabaashi and Karbowski, 2001).
  24.  Later stages of the infection were accompanied by membrane dysfunction (loss of ability to be plasmolysed) and progressive vacuolization of the cytoplasm.  Membrane damage was proposed to be the critical event for cell death. Apoptosis-related chromatin condensation and endo nucleolytic cleavage were not reported.  However, there was a gap in the time course in which these events may have occurred. Thus, the HR in this system has a subset of apoptotic features.  Further looking at a range of host–pathogen interactions using detailed time courses infers that apoptosis-related events such as mitochondrial swelling, chromatin condensation and endonucleolytic cleavage occur before general organelle dysfunction. This would be expected if the HR occurs by an apoptotic- like mechanism.
  25.  Although there is clear evidence that PCD occurs during plant development and environmental responses, the signals that trigger PCD in plants are unknown.  However, O2 - and H202 accumulate in senescing leaves (Pastori and del Rio, 1997). Thus, it is possible that ROS are a general trigger for PCD in plants.  Expression of a single gene is thought to be sufficient to trigger PCD in the megaspores of the fern Marsilea (Bell, 1996a), and it is possible that the product of such a gene could generate enough H2O2 to trigger PCD in several different kinds of plant cells (Demura and Fukuda, 1994).
  26. REPRODUCTIVE STAGE  Gametophyte development.  Megaspore cell death  Cell death of the nucellar tissue  Antipodal cell death  Tapetum cell death  Cell death in sex determination  Self-incompatibility-induced cell death. VEGETATIVE STAGE  Xylogenesis  Lateral Root Cap Differentiation  Aerenchyma Formation  Leaf Morphogenesis  Organ Abscission and Dehiscence  Leaf Senescence  Floral Organ Senescence
  27.  Autophagic PCD is characterized by cytoplasm vacuolization followed by the destruction of cell components by an intensive activation of lysosomal machineries. Autophagic features have been also found in different kinds of plant PCD.  In plants, the vacuole is responsible for lytic activity which leads to the removal of organelles and cell corpses.  In plants, different types of PCD play crucial roles in vegetative and reproductive development (dPCD), as well as in the reaction to environmental stresses (ePCD).  Forms of ePCD result in the sacrifice of cells in response to abiotic stresses, e.g., temperature or irradiation or biotic aggressors like pathogens (Wu et al. 2014).  Various dPCD events can be distinguished on the basis of their developmental context (Beers 1997).
  28.  dPCD is generally autolytic, as happens in xylem tracheary formation, where cytoplasm clearance is required for vessel functionality.  In fact, some research studies shown that autolytic events and PCD are actuated during tracheary element differentiation as separate processes with autolysis only occurring when PCD has terminated.  However, dPCD can also include autophagic features,as occurs during embryogenesis and germination processes.  ePCD is triggered by external insults which include pathogen attack as well as abiotic stress, such as heat stress, salinity, drought, and flooding.  In such cases, plants can activate a hypersensitive response (HR), which is a plant cell death activated against biotrophic pathogens at the site of attack
  29.  Plants activate PCD in senescent tissues, such as leaves, petals, sepals, in order to recycle nutrients before eliminating the tissues that are no longer required.  Differentiation-induced dPCD occurs as an inherent final differentiation step of particular cell types, e.g., xylem, anther tapetum, or root cap cells. Some cell types, however, can initiate dPCD in a facultative fashion.  Finally, age-induced dPCD occurs in all cell types of organs or even entire organisms as the end point of plant senescence.  dPCD and ePCD have traditionally been studied independently, and recent comparative analyses detected only limited similarity in their transcriptional signatures.
  30.  On the other hand, plants can fail to activate defense responses against abiotic stress and as consequence activate PCD.  This happens when the stress-dependent metabolic impairment overwhelms the plant’s ability to restore the physiological background and/or counteract the derived oxidative stress.  Abiotic stresses, such as drought, flooding, heat stress, and heavy metals in the soil, generally affect plant metabolism by restraining photosynthesis, reducing protein synthesis and thus protein turnover, and increasing electron flow in the respiratory chain into the mitochondria.
  31.  The impairment of all these pathways increases the production of reactive oxygen and nitrogen species (ROS and RNS) in the cell. When the plant fails to counteract the metabolic imbalance leading to the overproduced reactive species, it activates PCD.  Several plant hormones are also involved in the induction of both dPCD and ePCD: salicylic acid is required in HR cell death, ethylene in aerenchyma formation and tissue senescence, gibberellin in endosperm/aleurone development. 
  32.  Autophagy is a self-degradative process that is important for balancing sources of energy at critical times in development and in response to nutrient stress.  In addition to elimination of intracellular aggregates and damaged organelles, autophagy promotes cellular senescence and cell surface antigen presentation, protects against genome instability and prevents necrosis, giving it a key role in preventing diseases.  Greek meaning “Eating of cell”.  Coined by Christian Duve.  Self-degradative process..  Plays a house keeping role in removing misfolded or aggregated proteins, clearing damaged organelles and eliminating intracellular pathogens.  Its deregulation has been linked to non-apoptopic cell death
  33. APOPTOSIS  Pre programmed cell death.  Balances no. of cells in a multicellular organism.  Caused by oxidative stress, extrinsic or intrinsic signals etc.,.  Lysosomes are not involved.  Do not allow cell to survive.  Excessive apoptosis leads to atrophy. AUTOPHAGY  Self-degenerative process of its own components.  Balances the energy sources in the cell.  Caused by cellular stress like starvation, hypoxia etc.,  Lysosomes are involved.  Allows the cell to survive stress.  Excessive autophagy leads to cell death.
  34.  Will ‘Autophagic cell death’ applies to Programmed Cell Death (PCD) in plants..?  Possible role of autophagy as an executioner of programmed cell death (PCD) in plants.  Andrew Love et al.(2004) Suggested that autophagy is responsible for the bulk of cellular dismantling and remobilization of various compounds, during senescence, which is a type of developmental PCD  Developmental PCD in plants: The tonoplast becomes highly permeable (or ruptures); this results in the release of a massive amount of hydrolases, which rapidly degrade whatever is by then left of the cytoplasm, and in some cases also of the cell wall.  The action of hydrolytic enzymes, resulting in self-degradation, we proposed, can be regarded as a type of autophagy. The cell is after all ‘eating’ itself,
  35.  Micro-autophagy is the uptake of materials at the surface of a lytic vacuole. It occurs by the invagination or protrusion of the vacuolar membrane. The vesicles produced have only a single membrane.  Cacas and Diamond claimed that autophagic structures should possess a double membrane. This is not correct, as micro-autophagy is also autophagy and does not involve a vesicle with a double membrane.  They claim that autophagy has not been shown to be an executioner of plant PCD, therefore, cannot be based on the argument that no double-membrane structures have been observed during plant PCD.  Macro-autophagy starts further away from a lytic vacuole. In animal cells a portion of the cytoplasm, which can include various organelles, is surrounded by a growing double-membrane structure. Upon closure of the double membrane, the structure with its enclosed cytoplasmic material is an autophagosome.
  36.  In animals the outer membrane of the autophagosome subsequently fuses with a lysosome, a small vesicle containing hydrolases. This fusion results in degradation of the material inside the outer membrane of the autophagosome.  Upon fusion with a lysosome, the autophagosome is called an autolysosome. Yeasts also have autophagosomes, which fuse with a large lytic vacuole.  Macro-autophagy carried out by autophagosomes and autolysosomes is ubiquitous in animal cells. ‘Autophagic cell death’ in animals has been defined by the increase in the number of autophagosomes, autolysosomes and small lytic vacuoles produced by autolysosomes (together termed autophagic vacuolization) in the cytoplasm, independent of the process being a cause of death or only associated with death.  If macro-autophagy is defined as in animals (by the presence of autophagosomes and autolysosomes) it has not yet been demonstrated in plant cells.