Which of the following is/are anti-apoptotic genes?
Correct Answer: Bcl-2
Description: Ans. C. Bcl-2. (Ref. Robbins Basic Pathology 8th/ pg. Figure 1-23).Robbins Basic Pathology 8th/pg. Figure 1-23 ..........."If cells are exposed to growth factors and other survival signals, they synthesize antiapoptotic members of Bcl-2 family, the two main ones of which are Bcl-2 itself, Mcl-1 and Bcl-xL. These antagonize Bax, Bak and BIM, and thus limit the escape of mitochondrial pro-apoptotic proteins."1 MorphologyStimuli for apoptosisGenetic regulationPhysiologic examplesPathologic exaples# Cells shrink cytoplasm is dense and eosinophilic# Nuclear chromatin condenses, then fragments# Cell membrane blebs# Cell fragments (apoptotic bodies) are phagocytized by adjacent ceils or macrophages# Lack of inflammatory response# Cell injury and DNA damage# Lack of hormones, cytokines, or growth factors# Receptor-ligand signals:- Fas binding to fas ligand- Tumor necrosis factor (TNF) binding to TNF receptor 1 (TNFR1)# bcl-2 (inhibits apoptosis)# p-53 (stimulates apoptosis)# Selective death of lymphocytes in thymus# Embryogenesis - organogenesis and development# Hormone- dependent apoptosis (menstrual cycle)# Viral hepatitis (Counciliman body)# Cystic fibrosis (CF) - pancreatic atrophyMitochondria contain several proteins that are capable of inducing apoptosis; these proteins include cytochrome c and antagonists of endogenous cytosolic inhibitors of apoptosis. Cytochrome c, together with some cofactors, activates caspase-9, while other proteins block the activities of caspase antagonists that function as physiologic inhibitors of apoptosis. The net result is the activation of the caspase cascade, ultimately leading to nuclear fragmentation. If cells are exposed to growth factors and other survival signals, they synthesize antiapoptotic members of the Bcl-2 family, the two main ones of which are Bcl-2 itself and Bcl-xL. These proteins antagonize Bax and Bak, and thus limit the escape of mitochondrial pro-apoptotic proteins. Cells deprived of growth factors not only activate the pro-apoptotic proteins but also show reduced levels of Bcl-2 and Bcl-xL, thus further tilting the balance toward death.APOPTOSISIntrinsic pathwayInvolved in tissue remodeling in embryogenesis. Occurs when a regulating factor is withdrawn from a proliferating cell population (e.g., * 1L-2 after a completed immunological reaction>>apoptosis of proliferating effector cells). Also occurs after exposure to injurious stimuli (e.g., radiation, toxins, hypoxia). Changes in proportions of anti- and pro- apoptotic factors lead to*mitochondrial permeability and cytochrome c release. BAX and BAK are pro- apoptotic proteins; Bcl-2 is anti-apoptotic. Bcl-2 prevents cytochrome c release by binding to and inhibiting Apaf-1. Apaf-1 normally induces the activation of caspases. If Bcl-2 is overexpressed (e.g., follicular lymphoma), then Apaf-1 is overly inhibited, leading to*caspase activation and tumorigenesis.Extrinsic pathway2 pathways: - Ligand receptor interactions (FasL binding to Fas [CD95J) and immune cell (cytotoxic T-cell release of perforin and granzyme B) Fas-FasL interaction is necessary in thymic medullary negative selection. Mutations in Fas increase numbers of circulating self-reacting lymphocytes due to failure of clonal deletion.After Fas crosslinks with FasL, multiple Fas molecules coalesce, forming a binding site for a death domain-containing adapter protein, FADD. FADD binds inactive caspases, activating them.
Category:
Pathology
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