02/16c Cell Injury III - Apoptosis, Necrosis, and Cellular Aging Flashcards
What is necrosis? What are its causes and effects?
Morphologic expression of cell death, characterized by progressive disintegration of cell structure
Caused by overwhelming stress
Usually elicits an acute inflammatory response, often with the presence of neutrophils
What is apoptosis? By what features is it characterized?
Pathway of cell death induced by a tightly regulated suicide program and controlled by specific genes
Characterized by regular fragmentation of the nucleus and DNA, and formation of phagocytosis of apoptotic bodies
NO neutrophils are present
What are the ultimate consequences of necrosis vs. apoptosis?
Necrosis results in the loss of functional tissue and impaired organ function
Apoptosis results in the removal of damaged or unnecessary cells
What are five examples of physiologic apoptosis?
Embryogenesis and fetal development (e.g. hands and feet)
Hormone-dependent involution - regression of lactating breast after weaning
Cell loss in proliferating cell populations - immature lymphocytes, epithelial cells in the GI tract
Elimination of self-reactive lymphocytes
Death of cells that have served the function (neutrophils, lymphocytes)
What are four examples of pathologic apoptosis?
DNA damage due to radiation or chemotherapy
Accumulation of misfolded proteins leading to ER stress
Viral infections that induce apoptosis (HIV, adenovirus)
Organ atrophy after duct obstruction
What are the two pathways of apoptosis?
Extrinsic (death receptor) pathway
Intrinsic (mitochondrial) pathway
What stimulates the intrinsic apoptotic pathway? What molecules/signals are involved?
Lack of growth factor, DNA damage, or protein misfolding promotes the loss of Bcl-2 molecules
Loss of Bcl-2 causes increased mitochondrial membrane permeability, with release of Cytochrome c and other proteins that activate caspases
What are Bcl-2 molecules?
Anti-apoptotic molecules that are promoted by growth factors
What stimulates the extrinsic apoptotic pathway? What molecules/signals are involved?
Binding of extracellular ligands to TNF receptors or Fas receptors
This initiates the apoptotic signaling cascade
What is the major protein of the execution phase of apoptosis?
Caspase (cysteine-aspartic acid-proteases)
How do caspases disassemble a cell?
Cleave structural proteins, causing regular nuclear breakdown
Activate cytoplasmic DNase, which causes regular internucleosomal cleavage of DNA
What apoptotic mechanisms are implicated in Alzheimer’s, Parkinson’s, and Huntington’s disease?
Protein misfolding leading to ER stress, which can activate death receptors
What are the five major structural and biochemical changes that occur with cell aging?
Reduction of oxidative phosphorylation
Decreased synthesis of nucleic acid, structural proteins, enzymes, receptors, and transcription factors
Decreased capacity for nutrient uptake and DNA repair
Cytologic changes
Accumulation of misfolded proteins
What is replicative senescence?
The limited capacity of a cell to replicate
What is Werner’s syndrome?
Rare disease characterized by premature replicative senescence and accelerated aging
