Introduction to Disease: Cell Injury Flashcards

Question

Physiologic vs pathologic apoptosis

Answer 1

Physiological: important mechanism in development and normal cell turnover, removing redundant/damaged cells Pathological: eliminates potentially harmful cells (e.g. mutated or virally-infected cells)

Answer 2

1. mitochondrial intrinsic pathway | 2. death receptor extrinsic pathway

Answer 3

In the mitochondrial pathway, BH3-only proteins, which are related to members of the Bcl-2 family, sense a lack of survival signals or DNA or protein damage. These BH3-only proteins activate effector molecules that increase mitochondrial permeability. In concert with a deficiency of Bcl-2 and other proteins that maintain mitochondrial permeability, the mitochondria become leaky and various substances, such as cytochrome c, enter the cytosol and activate caspases. Activated caspases induce the changes that culminate in cell death and fragmentation. A specific feature of apoptosis is the activation of several members of a family of cysteine proteases named caspases. The process of apoptosis may be divided into an initiation phase, during which some caspases become catalytically active, and an execution phase, during which other caspases trigger the degradation of critical cellular components. Initiation of apoptosis occurs principally by signals from two distinct pathways: the intrinsic, or mitochondrial, pathway, and the extrinsic, or death receptor–initiated, pathway The Intrinsic (Mitochondrial) Pathway of Apoptosis This pathway of apoptosis is the result of increased mitochondrial permeability and release of pro-apoptotic molecules (death inducers) into the cytoplasm Mitochondria are remarkable organelles in that they contain proteins such as cytochrome c that are essential for life, but some of the same proteins, when released into the cytoplasm (an indication that the cell is not healthy), initiate the suicide program of apoptosis. The release of these mitochondrial proteins is controlled by a finely orchestrated balance between pro- and anti-apoptotic members of the Bcl family of proteins Growth factors and other survival signals stimulate production of anti-apoptotic proteins, the main ones being Bcl-2, Bcl-x, and Mcl-1. When cells are deprived of survival signals or their DNA is damaged, or misfolded proteins induce ER stress, sensors of damage or stress are activated. These sensors are also members of the Bcl family, and they include proteins called Bim, Bid, and Bad The sensors in turn activate two critical (proapoptotic) effectors, Bax and Bak, which form oligomers that insert into the mitochondrial membrane and create channels that allow proteins from the inner mitochondrial membrane to leak out into the cytoplasm. One of these proteins is cytochrome c, well known for its role in mitochondrial respiration. Once released into the cytosol, cytochrome c binds to a protein called Apaf-1 (apoptosis-activating factor-1 This complex is able to bind caspase-9, the critical initiator caspase of the mitochondrial pathway, and the enzyme cleaves adjacent caspase-9 molecules, thus setting up an auto-amplification process.

Answer 4

In the death receptor pathway, signals from plasma membrane. receptors lead to the assembly of adaptor proteins into a “death-inducing signaling complex,” which activates caspases, and the end result is the same. This pathway is initiated by engagement of plasma membrane death receptors on a variety of cells. Death receptors are members of the TNF receptor family that contain a cytoplasmic domain involved in protein-protein interactions that is called the death domain because it is essential for delivering apoptotic signals. The best-known death receptors are the type 1 TNF receptor (TNFR1) and a related protein called Fas (CD95) The ligand for Fas is called Fas ligand (FasL). When FasL binds to Fas, three or more molecules of Fas are brought together, and their cytoplasmic death domains form a binding site for an adapter protein that also contains a death domain and is called FADD (Fas-associated death domain). FADD that is attached to the death receptors in turn binds an inactive form of caspase-8 . . The enzyme then triggers a cascade of caspase activation by cleaving and thereby activating other pro-caspases, and the active enzymes mediate the execution phase of apoptosis

Answer 5

1. Cell shrinkage 2. Chromatin condensation: 3. Formation cytoplasmic blebs and apoptotic bodies 4. Phagocytosis apoptotic of bodies by macrophages or by healthy adjacent parenchymal cells.

Answer 6

The apoptotic cell appears as a round or oval mass of intensely eosinophilic with dense nuclear chromatin.

Answer 7

carcinoma with p53 mutations,or hormone dependent tumors – breast, prostate, ovary etc. Autoimmune disorders.

Answer 8

1) neurodegenerative diseases 2) ischemic injury and stroke. 3) virus-induced lymphocyte depletion.

Introduction to Disease: Cell Injury Flashcards

(33 cards)