Apoptosis Mechanisms and Functions

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Questions and Answers

What is produced during apoptosis that prevents damage to surrounding cells?

Apoptotic bodies (correct)

Cellular debris

Reactive oxygen species

Protein aggregates

Which component is essential in both intrinsic and extrinsic pathways of apoptosis?

FAS ligands

Caspases (correct)

BAX

Cytochrome C

What initiates the intrinsic pathway of apoptosis?

Cell stress recognized internally (correct)

Caspase activation

External signals from other cells

Inhibition of IAPs

Which proteins form pores in the mitochondrial membrane during apoptosis?

BAX and BAK Signup and view all the answers

What structure is formed when Cytochrome C combines with Apaf-1 during apoptosis?

Apoptosome Signup and view all the answers

What is the role of SMACs in apoptosis?

To bind to IAPs and promote cell death Signup and view all the answers

Which pathway of apoptosis is typically triggered by an immune cell signal?

Extrinsic pathway Signup and view all the answers

What is the fate of pro-caspase-3 during the apoptosis process?

It is cleaved into active caspase-3 by caspase-9. Signup and view all the answers

What is the primary purpose of apoptosis in multicellular organisms?

To remove damaged or unnecessary cells Signup and view all the answers

Which of the following factors can trigger apoptosis?

Genetic mutations and irreparable damage Signup and view all the answers

In the context of cell differentiation, what distinguishes pluripotent cells from unipotent cells?

Pluripotent cells can differentiate into any cell type, while unipotent cells can only become one specific type Signup and view all the answers

What is one of the key morphological changes that occurs in a cell undergoing apoptosis?

Nuclear fragmentation and chromatin condensation Signup and view all the answers

How do mitochondria play a role in the process of apoptosis?

They release factors that trigger the apoptotic pathway Signup and view all the answers

What occurs to a typical adult human in terms of cell loss due to apoptosis?

Approximately 50-70 billion cells per day Signup and view all the answers

What is the difference between apoptosis and necrosis?

Apoptosis is a planned cell death, while necrosis results from injury Signup and view all the answers

Which of the following statements best describes mesenchymal cells?

They can differentiate into muscle and connective tissues Signup and view all the answers

What is the role of the Fas receptor in apoptosis?

It binds to Fas ligand to initiate the death signaling complex. Signup and view all the answers

Which component is involved in the cleavage and activation of pro-caspase 8?

Fas-associated death domain (FADD) Signup and view all the answers

What initial mutation in normal cells can lead to cancer progression?

Mutation in proto-oncogenes that increases cell growth Signup and view all the answers

What occurs after the mutation that inactivates cell cycle checkpoints in cancer cells?

Uncontrolled cell growth and division Signup and view all the answers

What is metastasis in the context of cancer?

The spreading of cancer cells to different body parts Signup and view all the answers

What role do (proto)oncogenes play in cancer?

They are cancer activating genes. Signup and view all the answers

Which of the following pathways is NOT directly involved in the Fas-mediated apoptosis mechanism?

Cytochrome C release Signup and view all the answers

Cleavage of which protein by caspase 8 indicates the activation of the extrinsic apoptosis pathway?

Bid Signup and view all the answers

What typically occurs alongside mutations in oncogenes in cancer cells?

Loss of expression of tumor suppressor genes Signup and view all the answers

What is the primary role of housekeeping genes?

Maintaining essential cellular functions Signup and view all the answers

In which type of cells are genes A, B, and C expressed?

In both neurons and osteocytes Signup and view all the answers

What is a result of differential gene expression in neurons compared to osteocytes?

Distinct protein structures lead to different functions Signup and view all the answers

Which of the following correctly describes the changes in gene expression between neurons and osteocytes?

Genes A is on in neurons but off in osteocytes Signup and view all the answers

What aspect of cancer cell growth is linked to additional mutations?

Uncontrolled cell growth and division Signup and view all the answers

Which type of genes are involved in the basic maintenance of cellular life, such as DNA replication?

Housekeeping genes Signup and view all the answers

What is the main function of oncogenes in normal cell cycles?

To enhance cell growth and division Signup and view all the answers

What is the main characteristic of pluripotent stem cells?

They can differentiate into any cell type in the body. Signup and view all the answers

What happens during the process of cell determination?

It progressively fixes the fate of a cell's descendants. Signup and view all the answers

Which type of stem cell can differentiate into most but not all cell types?

Multipotent Signup and view all the answers

What is the final step in the process of stem cell differentiation?

Cell specialization Signup and view all the answers

In the context of stem cells, what does the term 'potency' refer to?

The range of differentiation potential a stem cell possesses. Signup and view all the answers

What distinguishes totipotent stem cells from pluripotent stem cells?

Totipotent stem cells can form any cell type including extra embryological tissues. Signup and view all the answers

What is a significant outcome of the differentiation process in stem cells?

Differentiated cells may change significantly in appearance and function. Signup and view all the answers

What notable contribution did Ian Wilmut and his team make to stem cell research?

They cloned a sheep using the nuclei from a mammary gland cell. Signup and view all the answers

What is a key feature of differentiated cells?

They have specialized functions within tissues. Signup and view all the answers

What is the primary function of adult stem cells in the body?

To replace damaged cells and repair tissue Signup and view all the answers

Which type of stem cells are most commonly used clinically?

Mesenchymal stem cells and haematopoietic stem cells Signup and view all the answers

What is a significant disadvantage of using adult stem cells?

Limited differentiation potential Signup and view all the answers

Which factors are commonly used to induce pluripotency in mature cells to create iPSCs?

OCT4, SOX2, KLF-4, c-MYC Signup and view all the answers

What is a potential risk associated with induced pluripotent stem cells (iPSCs)?

Tumorigenic potential Signup and view all the answers

What is indicated by the age/mutation risk associated with adult stem cells?

They may undergo mutations leading to reduced efficacy. Signup and view all the answers

Which describes an autologous stem cell transplant?

Stem cells harvested from the same individual Signup and view all the answers

What is a common application of induced pluripotent stem cells (iPSCs)?

Disease modeling and drug discovery Signup and view all the answers

Study Notes

Cell Function: Cell Death and Differentiation

The course is Fundamentals of Human Biology (FUNBIO.15)
The lecturer is Tom Hodgkinson
The date is 29/10/24
Learning Outcomes:
- Describe the process of cell death or apoptosis.
- Define the role of mitochondria in apoptosis.
- Understand cell differentiation, and the concept of unipotent and pluripotent cells.
- Describe the role of organelles in cell differentiation and tissue formation.
- Explain cellular processes triggered in cancer cell formation.
- Define mesenchymal cells and their differentiation into muscle and connective tissue.
- Differentiate between adult and embryonic stem cells.
- Discuss the ethical issues involved in stem cell research.

Circumstances for Cell Death (Apoptosis)

Genetic mutation/damage
Irreparable damage (radiation, chemical injury, pathogenic attack)
Cell stress (e.g., heat, pH changes)
Cell death induced by cytotoxic T cells or death receptors
Mitochondrial stress/injury
Injury to cell membrane
Growth factor/hormone gradients (e.g., embryonic development)
Cell cycle dysregulation (e.g., cancer)

Apoptosis- Programmed Cell Death

Necrosis is traumatic cell death from acute cellular injury.
Apoptosis is a highly regulated, controlled process of cell death.
Nobel Prize (2002) awarded to Brenner, Horvitz, and Sulston for work identifying genes controlling apoptosis
Occurs in multicellular and some single-celled eukaryotic organisms, like yeast.
Biochemical events produce characteristic cell morphology changes leading to death.
Involves cell shrinkage, chromatin condensation, blebbing, DNA condensation, mRNA decay, nuclear fragmentation, and organelle collapse.
Results in apoptotic bodies that are engulfed by phagocytes preventing cell contents release and damage to surrounding cells.
An average adult loses 50-70 billion cells daily due to apoptosis.
Apoptosis is crucial during development (e.g., separation of fingers and toes).

Mechanisms of Apoptosis

Apoptosis can occur via two pathways:
- Intrinsic pathway: the cell senses internal stress and kills itself.
- Extrinsic pathway: the cell kills itself due to signals from other cells.
Both pathways activate proteases called caspases.
Caspases lead to indiscriminate protein degradation.

Intrinsic Pathway (Mitochondrial Pathway)

Mitochondria are vital for multicellular life, especially aerobic respiration.
Some apoptotic pathways centre on mitochondria.
Mitochondrial changes include increased membrane pores, pore formation, and dissipation of mitochondrial membrane potential.
Important proteins in this pathway include Bax, Bak, cytochrome C. Also involved are Apaf-1/apoptosome procaspase 9, and caspase 3.

Extrinsic Pathway

An external signal (typically from immune cells) triggers this pathway.
Two main models are present: TNFP-induced and Fas-FasL-mediated.
FAS receptor binds to the Fas ligand (FasL), forming a death-inducing signaling complex (DISC). This activates caspase 8.
Caspase-8 can then truncate Bid, leading to apoptosis.
There's a connection between TNF-α and apoptosis, significant in autoimmune diseases.

Cancer Cell Formation

Normal cells have tightly regulated mechanisms preventing uncontrolled growth and division.
Disruption of these mechanisms are factors in cancer formation.
Cancer cells divide and grow unchecked, forming tumors or neoplasms.
Metastasis is the spread of cancer cells to different parts of the body.
Gene mutations can occur in proto-oncogenes (activating genes) and tumor suppressor genes.

Same Genome - Diverse Function

Cells with the same genome can have very different structures and functions depending on gene expression.
Gene expression differs based on the proteins produced by specific genes.

Differential Gene Expression

Gene expression means genes code for a protein.
Differential expression means different proteins are made in different cells, even from the identical DNA structure.
"Housekeeping genes" are essential for basic cellular functions.

How Does a Cell Decide?

Micro-environment (cell-cell/cell-extracellular matrix interactions, soluble factors, mechanical factors) plays a role.
Lineage commitment of parent cells, and DNA packaging/epigenetics, are key processes in controlling gene expression.

Stem Cell Determination & Differentiation

Stem cells are undifferentiated: they can self-renew and differentiate into other cells.
Potency describes the stem cell's differentiation potential.
Totipotent stem cells can form any cell type; Pluripotent cells potentially any body cell type and Embryonic stem cells are an example.
Multipotent cells can form specialized cell types within a specific lineage.
Unipotent cells differentiate into a single, specified cell type.
Differentiation is a genetic commitment to a specific cell type progression.

Different Types of Stem Cells

Adult stem cells in various tissues (bone marrow, adipose, etc.) are used clinically.
They can replace damaged cells and maintain tissue, however have limited differentiation potential.
Induced pluripotent stem cells (iPSCs): researchers can reprogram mature cells into a pluripotent state using transcription factors.
iPSCs share many properties with embryonic stem cells but with potential differences.

Stem Cells in the Clinical Scenario

Stem cells are used in autologous/allogeneic transplantations.
Autologous (most common) is using your own stem cells; allogeneic is using someone else's.
Treatments like chemotherapy use stem cells to replace destroyed blood cells.

Human Embryonic Stem Cells

ES cells are pluripotent and can differentiate into many cell types potentially.
Potential applications include regenerative medicine, disease modeling (for drug testing and development), and drug discovery.
However, ethical concerns (embryo destruction), and immune rejection are present.

Unregulated ES Application and Teratoma Formation

Teratomas are tumors consisting of cells from multiple germ layers.
Uncontrolled growth in pluripotent cells (e.g., ES cells) can result in teratoma formation.

Ethical Questions in Human Cloning

Human reproductive cloning attempts to create a genetically identical person.
Human therapeutic cloning aims to make ES cells or iPSCs for medical purposes.
Ethical issues include human dignity violations, unpredictable outcomes, and embryo destruction.

Induced Pluripotent Stem Cells (iPSCs)

iPSCs can be generated from adult cells like skin cells, urine cells, or blood cells, not from an embryo directly.
Re-programming them back to earlier states allows for creation of potentially valuable tools, therapies, and resources for research.
iPSCs face some limitations: factors such as genomic instability and tumorigenic potential exist and are a concern.

Learning Resources

Solomon Chapter 17, p362 (Developmental Genetics)
Science Articles (cited below)
Other online resources (cited below)

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Explore the intricate processes involved in apoptosis through this quiz. From the roles of cytochrome C to the intrinsic and extrinsic pathways, test your knowledge on how cells undergo programmed death. Understand the significance of apoptosis in maintaining homeostasis in multicellular organisms.