Cell Biology: Tissues, Necrosis, and Apoptosis

Flashcards about Tissues, Cell Death - Necrosis and Apoptosis Pathways - Intrinsic and Extrinsic, and Factors that Regulate Cell Survival and Division.

Tissues

Composed of cells and extracellular matrix, requiring mechanical support, innervation, and means of meeting the demands of life.

Factors Contributing to Tissue Stability

Cell communication, selective cell-cell adhesion, and cell memory.

Cancer Development by Accumulation of Mutations

Mutations in genes that control the cell cycle, apoptosis, metastasis, and telomere maintenance.

Cell Death

Cell death by injury (mechanical damage, toxic chemicals) or suicide (apoptosis - internal/external signals).

Necrosis

Cellular swelling, membranes broken, ATP depleted, cell lysis, and inflammatory reaction affecting whole tissue areas.

Apoptosis

Cellular condensation, membranes intact, ATP required, cell phagocytosis without tissue reaction, ladder-like DNA fragmentation affecting individual cells.

Why Cells Commit Apoptosis

Embryonic morphogenesis, sloughing of the uterus lining, formation of neuron connections, and regulation by hormones/growth factors.

What Makes A Cell Commit Apoptosis?

Withdrawal of positive signals (growth factors, IL-2) and receipt of negative signals (oxidants, DNA damage, death activators like TNF-α, Lymphotoxin, FasL).

The Apoptotic Pathway

DEATH Ligands, FADD, TRADD, FLIP, Bcl-2 family, Cytochrome c, p53, Mdm2, Caspases, many cellular proteins, DNA, growth factor Deprivation, Hypoxia, Loss of adhesion, Death receptors, Radiation, Chemotherapy

Caspases

A specialized protease that mediates apoptosis, cleaving substrates at specific sites, synthesized as zymogens and activated by other caspases.

Apoptosis as a Proteolytic Cascade

Amplifying cascade involving initiator and executioner caspases; executioner caspases cleave substrates responsible for cell death.

Key Targets of Proteolysis by Executioner Caspases

Inhibitor of DNAse fragmentation, Nuclear Lamins fragmentation of nucleus, Cytoskeleton Proteins - Disruption of Cytoskeleton & Cell Fragmentation.

Main Pathways Regulating Caspase Activation During Apoptosis

Mitochondrial mediated pathway (release of Cytochrome C) and Signaling through Death Receptors.

Bcl-2 Family

Regulate whether MOMP (Mitochondrial Outer Membrane Permeabilization) occurs; anti-apoptotic factors inhibit MOMP, while pro-apoptotic factors cause it.

Cell-Surface Death Receptors Regulate Extrinsic Pathway

Cell-surface receptors recruit adaptor proteins that bind and aggregate initiator procaspases upon ligand binding leading to a signaling cascade.

Mechanism of Survival Factors

Survival Factors by Signaling through Bcl2 family, Transcriptional activation of anti-apoptotic Bcl2 proteins, Akt kinase inactivates BH3-only pro-apoptotic proteins.

Extracellular Signals Required by Animal Cells

Stimulate cell division, stimulate growth, and suppress apoptosis.

Mitogens

Secrete signal proteins that bind to cell surface receptors activating signaling pathways to stimulate cell division (e.g., Rb).

G1 Cell Cycle Control

Mammalian cell G1-Cdk activity is mediated by transcriptional regulator E2F, regulated by Rb protein which inhibits cell cycle progression.

Malfunctions of Apoptosis Leading to Disease

Cancer, neurodegenerative diseases, AIDS, ischemic stroke, autoimmune disease.

Role in Diease - Neurodegeneration

Neurons are irreversibly post-mitotic, Death caused by lack of connection, growth factors or damage, lead to synaptosis or apopsosis.

Role in Disease - Cancer

Apoptosis eliminates damaged cells; most cancer cells are defective in apoptotic response. Leads to High levels of anti-apoptotic proteins or Low levels of pro-apoptotic proteins

Role in Disease, Aging

In Aging, degeneration is caused by too much accumlated oxidative damage, defective signals for cell repair, hyperplasia

What are the two main pathways that initiate apoptosis?

The intrinsic (mitochondrial) and extrinsic (death receptor) pathways.

How does the intrinsic pathway trigger apoptosis?

It is activated by intracellular signals such as DNA damage or cellular stress, leading to mitochondrial outer membrane permeabilization (MOMP) and release of cytochrome c.

What role does cytochrome c play in apoptosis?

Once released into the cytoplasm, cytochrome c activates caspases, the executioners of apoptosis.

How do survival factors prevent apoptosis?

They can increase the production of anti-apoptotic Bcl-2 family proteins or inactivate pro-apoptotic BH3-only proteins through the activation of the Akt kinase.

What is the role of IAPs (Inhibitor of Apoptosis Proteins)?

IAPs bind to and inhibit caspases, preventing them from executing apoptosis.

How can chemotherapeutic drugs induce apoptosis?

By damaging DNA or disrupting the cell cycle, triggering the intrinsic apoptotic pathway.

What is anoikis?

A form of apoptosis triggered by the loss of cell-matrix attachment, preventing cells from surviving in inappropriate locations.

How does p53 induce apoptosis?

In response to DNA damage, p53 can activate the transcription of pro-apoptotic genes, such as Bax, and inhibit anti-apoptotic genes, such as Bcl-2, ultimately leading to apoptosis.

What is the role of the proteasome in apoptosis?

The proteasome degrades proteins involved in cell survival, and its inhibition can trigger apoptosis.

What is the role of caspases in apoptosis?

Caspases are a family of proteases that play a crucial role in apoptosis. They are responsible for cleaving various cellular substrates, leading to the dismantling of the cell.

How are caspases activated during apoptosis?

Caspases are synthesized as inactive zymogens (pro-caspases) and are activated through proteolytic cleavage, often by other caspases, in a cascade-like manner.

What are initiator caspases?

Initiator caspases are activated by upstream apoptotic signals and, in turn, activate executioner caspases.

What are executioner caspases?

Executioner caspases are activated by initiator caspases and are directly responsible for cleaving cellular substrates, leading to cell death.

What is the significance of the caspase cascade?

The caspase cascade provides a rapid and irreversible mechanism for dismantling the cell during apoptosis.

How does the intrinsic (mitochondrial) pathway lead to caspase activation?

The intrinsic pathway triggers the release of cytochrome c from mitochondria, which then activates the caspase cascade through the formation of the apoptosome.

How does the extrinsic (death receptor) pathway lead to caspase activation?

The extrinsic pathway involves the activation of death receptors on the cell surface, which then recruit adaptor proteins and activate caspases.

What is the role of the apoptosome in apoptosis?

The apoptosome is a complex formed in the intrinsic pathway that activates caspase-9, an initiator caspase.

What is the function of IAPs (Inhibitor of Apoptosis Proteins)?

IAPs are a family of proteins that inhibit apoptosis by binding to and inhibiting caspases.

How do anti-apoptotic proteins like Bcl-2 prevent apoptosis?

Anti-apoptotic proteins like Bcl-2 inhibit the release of cytochrome c from mitochondria, preventing the activation of the caspase cascade.

How do pro-apoptotic proteins like Bax and Bak promote apoptosis?

Pro-apoptotic proteins like Bax and Bak promote the release of cytochrome c from mitochondria, triggering the activation of the caspase cascade.

How does p53 promote apoptosis?

p53, a tumor suppressor protein, can induce apoptosis in response to DNA damage by activating pro-apoptotic genes and inhibiting anti-apoptotic genes.

What is the role of death receptors in the extrinsic apoptotic pathway?

Death receptors, such as Fas and TNF receptors, initiate the extrinsic apoptotic pathway when they bind to their ligands (e.g., FasL and TNF-${\alpha}$).

How does DNA damage trigger apoptosis?

DNA damage can trigger apoptosis through the activation of the intrinsic pathway, often involving the tumor suppressor protein p53.

What is anoikis, and why is it important?

Anoikis is a form of apoptosis triggered by the loss of cell-matrix attachment. It prevents cells from surviving and proliferating in inappropriate locations.

How do chemotherapeutic drugs induce apoptosis in cancer cells?

Chemotherapeutic drugs can induce apoptosis by damaging DNA, disrupting the cell cycle, or targeting other cellular processes, ultimately triggering the apoptotic pathways.

What is the role of the proteasome in regulating apoptosis?

The proteasome degrades proteins involved in cell survival, and its inhibition can trigger apoptosis, particularly in cancer cells.