37.2
Apoptosis
Apoptosis is a combination of two Greek words, 'apo'and 'ptosis,'meaning separation and falling off, respectively. Hippocrates used this word to descr…
Apoptosis is a programmed cell death process where specific signals lead to the death of unwanted or potentially harmful cells.
The intrinsic or mitochondrial-mediated apoptotic pathway is triggered by intracellular death signals produced due to DNA damage, hypoxia, and biochemical stress such as oxidative stress. In contrast, the extrinsic apoptotic pathway is initiated when extracellular death-inducing ligands, such as cytokines, bind to the death receptors present on the cell surface.
The key mediators of apoptosis are proteases called caspases. Initiator caspases are activated by both intrinsic and extrinsic apoptotic pathways through different mechanisms.
Each initiator caspase then activates multiple executioner caspases.
In both pathways, the activated executioner caspases cleave cellular proteins causing morphological changes, such as cell shrinkage, nuclear fragmentation, and plasma membrane blebbing.
Next, the cellular components are enclosed into membrane vesicles called apoptotic bodies, which are then engulfed by phagocytic cells.
Through these steps, apoptosis results in controlled and contained cell death without causing inflammation and damage to the neighboring cells.
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Q1: What are the two main pathways that trigger apoptosis in cells?
Apoptosis is initiated through two distinct pathways. The intrinsic or mitochondrial-mediated pathway is triggered by intracellular death signals from DNA damage, hypoxia, and oxidative stress. The extrinsic apoptotic pathway is initiated when extracellular death-inducing ligands, such as cytokines, bind to death receptors on the cell surface. Both pathways ultimately activate caspases to execute cell death.
Q2: How do caspases function in the apoptotic process?
Caspases are proteases that serve as key mediators of apoptosis. Initiator caspases are activated by both intrinsic and extrinsic signals through different mechanisms. Each activated initiator caspase then activates multiple executioner caspases, which cleave cellular proteins. This cleavage causes morphological changes including cell shrinkage, nuclear fragmentation, and plasma membrane blebbing.
Q3: What morphological changes occur during apoptosis?
During apoptosis, cells undergo distinct morphological changes as executioner caspases cleave cellular proteins. These changes include cell shrinkage, nuclear fragmentation, and plasma membrane blebbing. Subsequently, cellular components are enclosed into membrane vesicles called apoptotic bodies. This controlled process prevents the release of potentially damaging molecules to neighboring cells.
Q4: How are apoptotic bodies removed from tissues?
After cellular components are enclosed into membrane vesicles called apoptotic bodies, these structures are engulfed by phagocytic cells through phagocytosis of apoptotic cells. This removal process is essential for maintaining tissue integrity and preventing inflammation. The contained nature of apoptosis ensures that neighboring cells remain unharmed during this controlled cell death.
Q5: Why is apoptosis important for maintaining normal tissue function?
Apoptosis allows cells to die in a controlled manner that prevents damage to surrounding tissues. Many internal checkpoints monitor cell health, and if abnormalities are detected, cells can spontaneously initiate apoptosis. This regulated process is essential for maintaining normal physiology and tissue homeostasis. Without proper apoptosis, cells may proliferate uncontrollably, as occurs in cancer.
Q6: What happens when cells lose contact with the extracellular matrix?
Normal animal cells have receptors that interact with the extracellular matrix, a network of glycoproteins providing structural support. When cells bind to this matrix, signaling cascades are initiated within the cell. However, if a cell moves away from the extracellular matrix, signaling ceases and the cell undergoes apoptosis. This system prevents uncontrolled cell proliferation and metastasis.
Q7: What diseases result from dysregulated apoptosis?
Dysregulated apoptosis leads to various diseases depending on whether apoptosis is decreased or increased. Decreased apoptosis contributes to cancer and cardiovascular diseases, allowing abnormal cells to survive. Increased apoptosis occurs in autoimmune diseases such as Hashimoto's thyroiditis, systemic lupus erythematosus, and rheumatoid arthritis, where healthy cells are destroyed.