Summary of Radiobiology: Radiation Physics and Biological Effects
Radiobiology: Radiation Physics and Biological Effects Explained
Introduction
Apoptosis is a form of programmed cell death that allows multicellular organisms to remove unwanted or damaged cells in a controlled way. Unlike accidental cell death (necrosis), apoptosis is an orderly process that prevents inflammation and preserves tissue health.
Definition: Apoptosis is a genetically regulated process of cell suicide that leads to characteristic morphological and biochemical changes and to the removal of cells without provoking an inflammatory response.
Key morphological features
Apoptosis can be recognized by a set of characteristic changes in cell structure and biochemical processing:
- Chromatin condensation (pyknosis): The cell's chromatin becomes densely packed and marginates along the nuclear membrane.
- Membrane blebbing: Small balloon-like protrusions form on the cell surface.
- DNA fragmentation (DNA laddering): Endonucleases cut DNA into regular internucleosomal fragments visible as a ladder on gel electrophoresis.
- Apoptotic bodies: The cell breaks into membrane-enclosed fragments that are phagocytosed by neighboring cells or macrophages.
Definition: Pyknosis is the condensation of chromatin in the nucleus of a cell undergoing apoptosis.
Molecular steps (broken down)
Initiation
- Intrinsic (mitochondrial) pathway: Triggered by internal stresses (e.g., growth factor withdrawal, oxidative stress). Key event: mitochondrial outer membrane permeabilization (MOMP) and release of cytochrome c.
- Extrinsic (death receptor) pathway: Triggered by extracellular ligands binding death receptors (e.g., Fas ligand to Fas receptor).
Signal transduction
- Adaptor proteins assemble at activated receptors or at the apoptosome (intrinsic pathway) and recruit initiator caspases.
- Initiator caspases (e.g., caspase-8, caspase-9) become activated and cleave downstream targets.
- Executioner caspases (e.g., caspase-3, caspase-7) dismantle cellular components, activating endonucleases and proteases.
Definition: Caspases are cysteine-aspartic proteases that cleave specific protein substrates to drive the apoptotic program.
Clearance
- Apoptotic cells expose “eat-me” signals such as phosphatidylserine on the outer leaflet of the plasma membrane.
- Phagocytes recognize and engulf apoptotic bodies, preventing leakage of intracellular contents.
Table: Intrinsic vs Extrinsic pathways
| Feature | Intrinsic pathway | Extrinsic pathway |
|---|---|---|
| Trigger | Internal stress (e.g., DNA damage, ER stress) | External ligand-receptor interactions (e.g., FasL–Fas) |
| Key organelle | Mitochondria | Plasma membrane receptors |
| Key initiator caspase | Caspase-9 | Caspase-8 |
| Major event | MOMP and cytochrome c release | Death-inducing signaling complex (DISC) formation |
| Regulators | Bcl-2 family proteins (pro- and anti-apoptotic) | FLIP, ligand availability |
Important regulators and signals
- Bcl-2 family: Balance between pro-apoptotic (e.g., Bax, Bak, Bid) and anti-apoptotic (e.g., Bcl-2, Bcl-xL) determines mitochondrial integrity.
- IAPs (inhibitor of apoptosis proteins): Bind and inhibit caspases.
- p53: A transcription factor that promotes apoptosis in response to severe cellular stress.
Practical examples and real-world applications
- Cancer therapy: Many chemotherapies and targeted agents aim to trigger apoptosis in cancer cells. Understanding which pathway is functional helps choose drugs that reactivate apoptosis.
- Developmental biology: Apoptosis sculpts tissues during development (e.g., removal of webbing between digits).
- Immune system: Apoptosis removes autoreactive lymphocytes, contributing to tolerance.
How apoptosis differs from necrosis (comparison)
| Aspect | Apoptosis | Ne
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Apoptosis Overview
Klíčová slova: Radiation interactions, DNA damage, Cell survival assays, Genetic disorders, Apoptosis
Klíčové pojmy: Apoptosis is programmed cell death with defined morphological changes, Chromatin condensation (pyknosis) and membrane blebbing are hallmark features, DNA laddering results from endonuclease cleavage into internucleosomal fragments, Intrinsic pathway involves mitochondrial outer membrane permeabilization and caspase-9, Extrinsic pathway is triggered by death receptors and activates caspase-8, Bcl-2 family proteins regulate mitochondrial integrity and apoptotic propensity, Annexin V and TUNEL are common assays to detect apoptosis, Caspase-3 and caspase-7 are main executioner caspases that dismantle the cell, Apoptotic cells expose phosphatidylserine to signal phagocytic clearance, Apoptosis avoids inflammation, unlike necrosis, by containing cellular contents