Apoptosis Mechanisms and Pathways

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Questions and Answers

What characterizes the intrinsic pathway of apoptosis?

It involves the activation of caspases. (correct)

It results solely in membrane blebbing.

It is triggered by external death signals.

It requires endonuclease deactivation.

Which of the following biochemical changes occurs during apoptosis?

Fragmentation of chromatin. (correct)

Stabilization of the nuclear membrane.

Inhibition of membrane blebbing.

Activation of procaspases.

What is the role of caspases in the apoptotic process?

To activate endonucleases directly.

To prevent cell shrinkage.

To degrade nucleosomes only.

To cleave and degrade various proteins. (correct)

Which morphological change is associated with apoptosis?

Formation of apoptotic bodies. Signup and view all the answers

What initiates the signaling cascade in apoptosis?

Cleavage of procaspases into active caspases. Signup and view all the answers

What is a primary characteristic that distinguishes apoptosis from necrosis?

Apoptosis is a programmed and regulated form of cell death. Signup and view all the answers

Which of the following best describes the metabolic fate of cells undergoing apoptosis?

Cells shrink, and their DNA is fragmented into small units. Signup and view all the answers

What role does cytochrome c play in the apoptotic process?

It is released from mitochondria to initiate apoptosis. Signup and view all the answers

What is one physiological reason for the occurrence of apoptosis in multicellular organisms?

To remove potentially harmful cells that do not meet developmental criteria. Signup and view all the answers

What type of response does apoptosis elicit in neighboring cells?

No response, as it ensures neighboring cells remain unaffected. Signup and view all the answers

Which type of cell death is characterized by an inflammatory response and is often associated with infection?

Pyroptosis Signup and view all the answers

Which cellular process is believed to contribute to cancer through the evasion of apoptosis?

Autosis Signup and view all the answers

What triggers the extrinsic pathway of apoptosis during ischemia-reperfusion injury?

Atrioscarotic clot Signup and view all the answers

Which gene is an example of a tumor suppressor gene that plays a critical role in cancer development?

P53 Signup and view all the answers

Which type of cell death results in cellular degradation without initiating inflammation?

Apoptosis Signup and view all the answers

What effect does the inactivation of tumor suppressor genes typically have on cell proliferation?

It increases the rate of cell division. Signup and view all the answers

Which gene is associated with retinoblastoma and small-cell lung carcinoma?

Rb1 Signup and view all the answers

Which of the following describes the function of the p53 protein?

Activates transcription of the p21 gene. Signup and view all the answers

What is the primary consequence of mutations leading to an oncogene from a proto-oncogene like ras?

It becomes always activated, stimulating proliferation. Signup and view all the answers

Which type of cancer is specifically associated with the BRCA2 gene?

Breast/ovarian tumors Signup and view all the answers

In the context of apoptosis, what is a primary difference between apoptotic cell death and necrosis?

Apoptotic cells avoid leakage of intracellular contents. Signup and view all the answers

What role does telomerase play in the aging of cells?

It maintains telomere length and impacts cell aging. Signup and view all the answers

What is the primary function of the DCC gene in the context of colorectal cancer?

It is involved in cell surface interactions. Signup and view all the answers

Which of the following statements about apoptosis is accurate?

Deficient apoptosis can lead to autoimmune disorders. Signup and view all the answers

In which scenario is autophagy generally considered protective?

Under conditions of environmental stress. Signup and view all the answers

What distinguishes necroptosis from necrotic cell death?

Necroptosis can be inhibited by RIP1 kinase inhibitors. Signup and view all the answers

Which of the following best describes autophagic cell death?

Involves extensive cytoplasmic vacuolization. Signup and view all the answers

What role does necroptosis play in viral infections?

It causes rapid membrane permeabilization. Signup and view all the answers

What is one consequence of autophagy inhibition in developmental processes?

Inhibits developmental cell death. Signup and view all the answers

What condition is NOT typically associated with excess apoptosis?

Organ regeneration. Signup and view all the answers

Which factor has been linked to necroptosis during pathophysiological events?

RIP1 kinase. Signup and view all the answers

Which of the following correctly describes the activation process of caspases?

Proteolytic cleavage involving removal of prodomain and linker region Signup and view all the answers

What role do death receptors play in the extrinsic apoptotic pathway?

They mediate ligand-induced trimerization leading to caspase activation. Signup and view all the answers

Which proteins are known to interact primarily in the intrinsic apoptotic pathway?

Bax and Bcl2 Signup and view all the answers

What is a critical function of cytochrome c in the intrinsic pathway?

Indirectly promotes the assembly of the apoptosome Signup and view all the answers

What does the term 'induced proximity' refer to in the context of apoptosis?

The essential spatial arrangement of proteins leading to caspase activation Signup and view all the answers

What method can be used for detecting nuclear DNA fragmentation in apoptosis assessment?

TUNEL staining Signup and view all the answers

Which combination of ligands and receptors is correctly matched in the context of apoptosis?

FasL - Fas (CD95) Signup and view all the answers

What role do IAPs play in the apoptotic process?

Inhibit the function of caspases Signup and view all the answers

How many family members of caspases are there?

More than 14 Signup and view all the answers

Which specific step marks the assembly of caspases into an active enzyme complex?

Formation of a tetramer with two catalytic sites Signup and view all the answers

Study Notes

Cell Death & Apoptosis

Cell death is a vital process in maintaining a constant number of cells within the body.
Two major forms of cell death include apoptosis (programmed cell death) and necrosis (killing, decay, and destruction).
Apoptosis is a tightly regulated, controlled process that eliminates unwanted or damaged cells without causing inflammation to surrounding cells.

Apoptosis in Development & Diseases

Embryonic development heavily relies on apoptosis.
During development, apoptosis eliminates cells to sculpt tissues and organs into their proper shapes.
Apoptosis is crucial for proper immune function, removing immune cells that don't pass regulatory tests.

Objectives

Understanding various cell death pathways.
Assessing cell death mechanisms.
Delving into the physiological process of apoptosis.
Exploring the association between apoptotic pathway defects and diseases.

Cell Death

The body maintains a stable cell count by eliminating cells when necessary.
Apoptosis is cell suicide, a programmed cell death.
Necrosis is cell death characterized by cell killing, decay, and destruction.

Embryonic Development

Embryonic development involves programmed cell death.
Apoptosis sculpts an embryo into its final form.
Examples include processes such as the absorption of the tadpole's tail.

Adult Cell Death

Billions of healthy cells are lost via apoptosis every hour in adults.
Regulation of cells removed.
Controls during development prevent damaged cells from proliferating.

Apoptosis Publications/Year

The number of publications regarding apoptosis increased significantly over time, with a notable rise towards the late 1990s.

Apoptotic Pathways

Illustrates apoptotic signalling, pathways, and details.
- C. elegans apoptosis
- Drosophila apoptosis
- Mammalian apoptosis

Nobel Prize in Physiology/Medicine 2002

Sydney Brenner, H. Robert Horvitz, and John Sulston shared the 2002 Nobel Prize for their genetic regulation of organ development and programmed cell death.

Apoptotic Changes

Morphological changes in apoptosis include cellular shrinkage, nuclear fragmentation, and formation of apoptotic bodies.
Biochemical changes during apoptosis involve caspase activation and endonuclease activation.

Apoptosis Results

Apoptosis produces a swift, clean death of cells without harming nearby cells or triggering an immune response.
DNA fragmentation is a hallmark of the process.
Key features include cell shrinkage, mitochondrial cytochrome c release, and altered plasma membrane.

Death by Injury vs. Death by Suicide (Necrosis vs. Apoptosis)

Key visual representations compare apoptosis (a controlled and distinct process with preserved membrane integrity) versus necrosis (a disordered and destructive process with compromised membrane integrity).
Apoptosis's morphological features and biochemical pathways are compared and contrasted with necrosis.

What is Apoptosis?

Apoptosis is programmed cell death.
It involves cellular condensation and no tissue reaction.
Membranes remain intact in apoptosis.
In apoptosis, DNA fragments create a ladder-like pattern.
In vivo, apoptosis involves individual cells.
Necrosis involves cellular swelling and broken membranes.
In necrosis, ATP is depleted and there's an inflammatory reaction.
DNA fragmentation is random or smeared in necrosis.
Whole areas of tissue are affected in necrosis.

Morphological Differences in Apoptosis and Necrosis

Necrosis involves chromatin clumping, swollen organelles, and flocculent mitochondria.
Apoptosis involves mild convolution, chromatin and cytoplasmic condensation, nuclear fragmentation, apoptotic bodies, phagocytosis, and no inflammation.

Necrosis

Necrosis is the process of irreversible cell damage and occurs due to harmful factors.
Progressive changes from normal cells include disaggregation of polysomes, focal chromatin margination, and mild mitochondrial swelling.
Irreversible changes lead to high amplitude mitochondrial swelling, mitochondrial matrix intensification, and progressive endoplasmic reticulum dilation.
The process involves lysosomal rupture and impairment of plasma membrane integrity.
Eventually, recognizable cellular organelles are lost.

What Makes a Cell Commit Suicide?

Cells commit suicide due to signals like loss of positive signals (e.g., growth factors, TNF-α), presence of negative signals (e.g., DNA damage), and other stimuli.

Steps in Apoptosis

Decisions to initiate apoptosis, the actual cell death process, engulfment of remaining parts by immune cells, and final degradation of the cell are part of the process.
This involves condensing the nucleus, fragmenting the cytoplasm, and creating apoptotic bodies.
DNA fragments into nucleosomes.

Apoptotic Signaling

Illustrates various stimuli, signals, regulators, and effectors involved in apoptotic signaling pathways.
Key proteins and processes, including those that promote life or death in cellular contexts, are highlighted.

Apoptosis: Morphology

Depicts the steps of apoptosis, including membrane blebbing, mitochondrial leakage, nuclear fragmentation, and chromatin condensation.

Biochemical Changes in Apoptosis

Initiates via caspase activation and continues with the activation of endonucleases..
Caspases, cysteine proteases, are essential for apoptosis as inactive precursors activated by other proteins following the appropriate signal.

Caspases

Caspases are proteases involved in apoptosis.
These proteases are crucial for degradation of cellular components.
Often present as inactive procaspases, which require other proteins to be activated.

Caspases (proteases)

A crucial role is taken by caspase proteases.
Caspase activation requires proteolytic cleavage.
Key steps include removal of prodomains and linker regions, assembly into complexes of large and small subunits, and the subsequent formation of a tetramer.
Caspase family members number over 14.

Caspase Functions and Structure

Shows different caspase groups involved in apoptosis.
Key caspases (initiator/effector) are detailed in diagrams.

Apoptotic: Pathways - Extrinsic Pathway - Death Receptor Mediated

Visual description of the extrinsic pathway (death receptor mediated).
Presents steps of caspase activation using FADD, Fas receptor, and ligand interaction.

Apoptotic: Pathways - Intrinsic Pathway - Mitochondrial Mediated

Demonstrates the intrinsic pathway or mitochondrial pathway.
Steps of cytochrome c release, Apaf-1 activation, apoptosome assembly, and the resulting caspase cascade are explained.

Ligand/Death-Induced Cell Death

Presents a tabular format of the ligands and the receptors involved in cell death.
Explains the various pathways involved.

Ligand-Induced Cell Death

Death ligands (e.g., FasL, TRAIL) trigger cell death through interaction with death receptors.
Ligand binding leads to receptor trimerization.
Death domains and the activation of caspase 8 are key components of this process.

The Mitochondrial Pathway / Extrinsic Linking Intrinsic

Illustrates the intricacies of the mitochondrial pathway, encompassing connections to extrinsic pathways and growth factor receptors.
Shows the roles of p53, Bax, Bid, BAD, Bcl2, Apaf1, and cytochrome c in cell death regulation.

Assessing and Imaging Apoptosis

Explains methods for visually detecting or assessing apoptosis.
Illustrates microscopy and flow cytometry techniques as examples.

Detection of Apoptotic Changes in DNA

Discusses methods employed to detect apoptotic changes in DNA, including nucleic acid staining for morphological analysis, TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay to identify DNA fragmentation, and single-cell electrophoresis techniques or comet assays.

Importance of Apoptosis

Essential for physiological functions, development, and repair.
Defects in apoptosis can contribute to neurodegenerative diseases, cancer, and autoimmunity.

Other Forms of Cell Death

Presents several cell death methods besides apoptosis and necrosis.
- Autophagic cell death.
- Necroptosis .

Autophagic Cell Death

Autophagy (self-eating) as a survival or destructive mechanism in healthy or stressed cells.
Different steps in autophagy that lead to cell death or survival.

Necroptosis

Necroptosis as a programmed form of necrotic cell death.
Necroptosis is distinct in cell death mechanisms.
- rapid membrane permeabilization
  - release of cell contents.
  - exposure of damage-associated molecular patterns.

Apoptosis Excess

Discusses instances of apoptosis excess in ischemia-reperfusion injury, noting that initiator caspases and apoptosis of endothelial cells are central to this process.

Cancer and Apoptosis

Evasion of apoptosis can initiate cancer.
Activating apoptosis in cancer cells is a therapeutic strategy to eliminate cancer cells and combat uncontrolled proliferation.

Genes Playing Role in Cancer Development

Discusses the central role played by oncogenes, tumor suppressor genes, and DNA repair genes within the development of cancerous cells.

Functions of Cellular Proto-Oncogenes

Discusses specific proto-oncogenes and their signaling pathways, explaining how growth factors, receptors, and cytoplasmic signal transduction are involved.

Oncogenes

Proto-oncogenes mutate to form oncogenes, causing constitutive activation of signaling pathways, thus resulting in uncontrolled cell proliferation.
The mutated form (oncogene) of the ras proto-oncogene is a key example.

Tumor Suppressor Genes

Normally, tumor suppressor genes inhibit cellular proliferation, and loss-of-function mutations in these genes contribute towards cancer development.

p53 Tumor Suppressor Genes

p53 is a critical transcription factor that regulates cellular responses to DNA damage.
Its activation leads to cellular responses such as cell cycle arrest to repair DNA damage, and apoptosis if damage cannot be repaired.
p53 gene mutation or disruption affects its activation potential and contributes to unchecked cell proliferation—a primary characteristic of cancers.

Cancer Treatment/Therapies

Illustrates a complex network of cellular signaling pathways involved in cellular processes and cancer therapy.
Explains that numerous factors regulate the interactions in the network.

Promising Cancer Targets

Emphasizes key proteins or targets that are crucial to understanding and potentially treating specific cancers more effectively.
Illustrates interaction networks amongst several proteins to show the complex organization.

Apoptosis - Programmed Cell Death

Defines apoptosis as a process of programmed cell death where the cell destroys itself.
Differentiates apoptosis from necrosis, highlighting the distinct mechanisms through which cells die.
Introduces the concept of cellular signals that could trigger apoptosis.
Presents apoptosis-related components and the differences and similarities between mitogens, growth factors, and survival factors.
Examines specific cell cycle stages related to apoptosis.
Discusses how telomeres and telomerase affect aging and the possibility of using telomerase to prevent aging.
Highlights the existence or nonexistence of various human cell types and their functions.

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Description

This quiz explores the intrinsic and extrinsic pathways of apoptosis, focusing on the biochemical and morphological changes that occur during programmed cell death. Test your understanding of the role of caspases, cytochrome c, and the differences between apoptosis and necrosis, alongside their implications in health and disease.