APOPTOSIS PART 2 | Mechanism of apoptosis | PATHOLOGY | cell injury | with notes

Описание: This video, "APOPTOSIS PART 2 | Mechanism of apoptosis | PATHOLOGY | cell injury | with notes," by MEDEAZYBYLAKSHMI, details the molecular mechanisms of apoptosis, a form of programmed cell death (0:14).

The video divides apoptosis into two main phases (0:50):
Initiation Phase (0:55): This phase involves the activation of initiator caspases, primarily caspases 8, 9, and 10 (1:01). The video further breaks down the initiation phase into two pathways:
Extrinsic Pathway (Death Receptor-Initiated Pathway) (1:45): This pathway is triggered by extracellular signals and involves the binding of ligands (like FAS ligand or TNF-alpha) to death receptors (CD95 or FAS receptor) on the cell surface (2:08). This binding leads to trimerization of the receptors, which recruits adapter proteins (like FADD - FAS Associated Death Domain) that activate pro-caspases 8 and 10 into active caspases 8 and 10 (3:01).
Intrinsic Pathway (Mitochondrial Pathway) (3:36): This pathway is activated by intracellular stress signals such as DNA damage, growth factor deprivation, or nutrient deficiency (5:45). These stressors activate stress sensors (Bim, Bid, Bad, Noxa, Puma), also known as BH3-only proteins, which promote pro-apoptotic factors and inhibit anti-apoptotic factors (6:01). This leads to increased mitochondrial permeability and the release of cytochrome C into the cytoplasm (6:51). Cytochrome C then combines with Apoptosis Activating Factor (APAF1) to form an apoptosome, which activates pro-caspase 9 into active caspase 9 (7:00).
Execution Phase (9:37): In this phase, the activated initiator caspases (8, 9, 10) activate effector caspases (caspases 3, 6, 7), with caspase 3 being the most crucial (9:57). These effector caspases then activate enzymes like phospholipases, proteases, and endonucleases, leading to membrane damage, cytoskeleton breakdown, and DNA fragmentation, ultimately resulting in cell death (10:08).

The video also discusses:
BCL2 Family (7:30): This family of proteins regulates apoptosis, with anti-apoptotic members (e.g., BCL2, BCL-XL) preventing it, pro-apoptotic members (e.g., Bax, Bak) inducing it, and regulatory members (BH3-only proteins) balancing the process (7:37).
Apoptotic Bodies and Phagocytosis (10:30): Dying cells form apoptotic bodies, which signal macrophages to engulf them through phagocytosis (10:56). This process, called efferocytosis (12:34), involves the presentation of proteins like C1q, thrombospondin, and flipped phosphatidylserine on the surface of apoptotic bodies (11:21). The flipping of phosphatidylserine to the outer membrane is a key marker, and annexin V can be used to identify this (11:55).
Molecular Markers of Apoptosis (12:45): Key markers include CD95/FAS staining, a positive TUNEL stain, and a DNA electrophoresis "ladder pattern" (12:47).

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