Cell Death For,s Flashcards
What are the three main forms of cell death?
Necrosis: Traumatic cell death due to acute injury (e.g., hypoxia).
- Apoptosis: Programmed cell death (e.g., DNA damage, cytotoxic T-cell contact).
- Excitotoxicity: Neural tissue-specific cell death caused by disturbed glutamate homeostasis.
What are the characteristics of necrosis?
Membrane damage.
• Chromatin flocculation.
• Rapid depletion of energy levels.
• Leakage of cell contents causing inflammation.
What are the characteristics of apoptosis?
Intact membrane with blebbing (membrane protrusions).
• Chromatin condensation and nuclear shape distortion.
• Energy levels maintained or slowly depleted.
• No inflammation (engulfed by phagocytes before spilling contents).
What are the steps in apoptosis?
Chromatin condensation and membrane blebbing.
- Cell fragmentation into apoptotic bodies.
- Apoptotic bodies attract phagocytes via externalized phosphatidylserine.
- Phagocytes bind to receptors, stimulate anti-inflammatory cytokines, and engulf the dying cell.
What are common triggers for apoptosis?
DNA damage.
• Viral infection.
• Cancer cells.
• Developmental processes (e.g., metamorphosis).
• Self-tolerance (elimination of autoimmune lymphocytes).
What are biochemical markers of apoptosis?
DNA fragmentation creates a ladder pattern in gel electrophoresis.
• TUNEL assay detects free DNA ends by labeling with dUTPs.
• Phosphatidylserine externalization detected by Annexin V protein.
• Loss of mitochondrial electrochemical gradient measured with fluorescent dyes.
What enzymes drive apoptosis?
• Caspases: Proteases with cysteine active sites that cleave substrates at aspartate residues.
• Caspases are tightly regulated to prevent premature activation.
What are the two apoptotic pathways?
- Extrinsic Pathway:
• Triggered by extracellular signals.
• Death receptors bind ligands and activate caspases.
- Intrinsic Pathway:
• Stimuli cause mitochondrial membrane leakage.
• Cytochrome C release activates caspases
What role does UV radiation play in apoptosis?
UV-B (sunlight): Causes thymine dimers in DNA, leading to replication errors, mutations, and apoptosis (helps limit skin cancer).
• UV-C: Lethal, but absorbed by the ozone layer.
How does insufficient or excessive apoptosis cause disease?
Insufficient Apoptosis: Autoimmune diseases (failure to eliminate lymphocytes).
• Excessive Apoptosis: Diseases like type 1 diabetes mellitus.
What is excitotoxicity?
: A form of neural cell death caused by excessive glutamate, leading to prolonged receptor activation and intracellular calcium buildup.
Q12: How does glutamate homeostasis work?
Glutamate is synthesized from glutamine in the Krebs cycle.
• Released into the synaptic cleft for nerve impulses.
• Recycled back into cells via vesicular pumps.
Q13: What happens during disturbed glutamate homeostasis?
Excess glutamate is released (e.g., during hypoxia).
• Prolonged activation of NMDA and AMPA receptors leads to calcium entry.
• Ca2+-dependent enzymes degrade phospholipids and other biomolecules, causing cell death.
What clinical conditions are associated with excitotoxicity?
Stroke.
• Trauma.
• Neurodegenerative diseases.