Cell Bio Apop/Cell Cycle (6)

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  1. Hypertrophy
    an increase in cell size; also used to describe tissues and organs that have enlarged (NOT an altered proliferative state)
  2. altered Proliferation states that are REVERSIBLE:
    • Regeneration
    • Metaplasia
    • Hyperplasia
    • Dysplasia
    • • altered growth states in tissues can reverse back to normal or at least stop progressing if the stimulus that provoked the proliferation is removed
  3. Regeneration
    a one-for-one replacement of cells; type of reversible proliferation state
  4. Hyperplasia
    • increase in number of fully differentiated/functions cells in a tissue (more than normal; in response to some kind of stimulus, eg. injury)
    • • disease examples: Restenosis [following vascular surgery], Grave's disease
  5. Restenosis following vascular surgery
    • • if endothelial cells don’t regenerate quickly enough after a balloon angioplasty, then smooth muscle cells can become hyperplastic
    • • this is problematic b/c excessive smooth muscle cells causes re-blockage (restenosis) of the blood vessel that was JUST opened
  6. Grave's disease
    • • a form of hyperthyroidism
    • • hyperplasia occurs: too many thyroid cells that are all fully differentiated
    • • with the increase of cells comes an increase of thyroid hormone production --> leads to increased metabolic rate, weight loss, bulging eyes, and strabismus
  7. Hyperthyroidism
    • overproduction of thyroid hormones --> increased metabolic rate, increased ocular pressure
    • • Grave's Disease = most common form of hyperthyroidism
  8. Metaplasia
    adaptive substitution of one cell type by another cell type; ALWAYS pathogenic
  9. What are the two places metaplasia is commonly seen in?
    • 1) Lung – in smokers, heat and smoke cause normal cells to be replaced by other, more protective cells
    • 2) Cervix: Chronic Inflammatory Pelvic Disease
    • • normal columnar is replaced by a stratified squamous epithelium
    • • more protective squamous epithelium lacks cilia and can't move mucus along well creating a rich environment for bacterial/viral replication
  10. Dysplasia
    • changes in mitotic rate of cells, loss of positional control, and loss in the uniformity of cell shape (pleiotropy)
    • • often a precursor to cancer
    • • seen in the exocervix where it is often a precursor to CERVICAL CANCER (reason for pap smears)
  11. cancer
    malignant neoplasia or malignant tumor; cell has to lose both proliferation controls and positional controls to be cancerous
  12. Neoplasia
    • proliferation continues even in the absence of an external stimulus (NOT CANCER)
    • • NON-reversible proliferation state
  13. Benign Neoplasia
    • loss of proliferation control only; "benign" tumors, like fibroids
    • • when there the loss of proliferation control, but NO loss of position control; means that a tumor will result but can't spread
  14. Uterine Fibroids
    • clinical correlate: BENIGN NEOPLASIA
    • • these are benign tumors that grow in the uterus
    • • positional control is retained.
    • • tumors cause severe pain, bleeding and infertility
  15. Malignant Neoplasia
    • loss of BOTH proliferation and positional controls
    • • (eg. metastatic tumors, "cancer")
  16. Cancer
    clinical correlate: MALIGNANT NEOPLASIA
  17. CENTROMERES ARE ATTACHED TO __________ AND CYTOKINESIS IS ORCHESTRATED BY ____________
    Centromeres are attached to microTUBULES and cytokinesis is orchestrated by microFILAMENTS
  18. position of a cell within a tissue can determine its:
    • proliferation rate
    • • partly b/c information in the extracellular matrix helps regulate cell proliferation
    • • eg. epithelial cells in intestinal crypt
  19. What are the four phases of the cell cycle?
    • G1prepares cell for replicating DNA; cell is busy doubling its contents in preparation for an eventual cell division
    • S
    • G2
    • M
  20. G1
    prepares cell for replicating DNA; cell is busy doubling its contents in preparation for an eventual cell division
  21. Restriction (R) Point
    • checkpoint between G1 and S where the cell has the option to exit the cell cycle & enter a quiescent state called G0
    • • cells go into G0 based on their nutritional state, positional information, density/contact/ shape/stretch information, and matrix information
  22. Rb protein
    • normally inactive (hypophosphorylated) and complexed w/ TFs needed for cell proliferation
    • • this prevents them from binding to DNA
    • • during correct passage through the R checkpoint, cyclin D/cdk4-6 and cyclin E/cdk2 complexes phosphorylate Rb, changing its conformation and releasing the TFs
  23. Describe the active/inactive state of the Rb protein:
    • • active: UNphosphorylated, complexed with TFs
    • • inactive: phosphorylated, NOT complexed with TFs
    • • in tumor cells, the Rb protein is missing or defective.
  24. How does the R checkpoint work?
    • 1) external signals (growth factors) stimulate synthesis of cyclins D & E
    • • cyclin D partners w/ cdk4 or 6
    • • cyclin E partners w/ cdk2
    • 2) when enough cyclin D/cdk4-6 and cyclin E/cdk2 are activated, they phosphorylate Rb protein
    • 3) the TFs released from Rb bind to DNA and activate transcription that encodes proteins which push cells through the R-point --> into S-phase
    • • once DNA synthesis starts a protease is activated & destroys cyclins D & E inactivating kinase complexes
  25. S
    DNA replication
  26. G2
    prepares cell for segregation/division of genome and cytoplasm
  27. M
    chromosome segregation (mitosis) and separation of daughter cells (cytokinesis)
  28. What are the purposes of checkpoints in the cell cycle?
    • • monitor the health of the nuclear genome (i.e., DNA damage, completeness of DNA replication, alignment of chromosomes
    • • monitor availability of key nutrients and cytokines in the environment
  29. In what kind of cells is the R (restriction) point defective?
    CANCER cells; they plough through & if they start making DNA and don't have enough material they'll happily die
  30. MPF
    • regulates mitosis; made up of two cyclins: cyclin B & cdk1
    • • the key substrates for cyclin B-cdk1 are laminas and histones
    • • think back to lecture 1: at the start of mitosis, laminas are phosphorylated, causing nuc. membrane disassembly, while the histones are phosphorylated, cause chromosome CONdensation
  31. Which cyclin partners with which cdk?
    Image Upload 1
  32. Tissues with the greatest frequencies of ___ _________ also exhibit the greatest frequency of apoptosis
    • cell proliferation
    • • seen in thymus, spleen, small intestine, epidermis, & ovarian follicles
  33. Necrosis
    • •'accidental' cell death
    • •triggered by sustained ischemia, physical or chemical trauma (eg. ionic shock)
    • •cells and organelles swell, organelles damaged, •chromatin randomly degraded
    • •cells LYSE
    • •INFLAMMATORY RESPONSE OCCURS
  34. Apoptosis
    • •programmed cell death triggered by specific signals that activate specific genes
    • •cells shrink, organelles intact, & chromatin is degraded systematically
    • •membrane blebs (chunks of cell) can be phagocytosed by neighboring cells
    • •NO INFLAMMATORY RESPONSE
  35. PKD (polycystic kidney disease)
    • clinical correlate: APOPTOSIS
    • •autosomal dominant
    • •results in uncontrolled APOPTOSIS of kidney cells.
    • •get kidney tissue full of cysts b/c cells that have died from apoptosis leave spaces that become filled with fluid --> creating cysts.
  36. What are the 3 phases of Apoptosis?
    • 1) Induction: intrinsic or extrinsic
    • 2) Modulation
    • 3) Execution: caspases --> endonucleases
    • (I'm Meredith Elman)
  37. What are PHYSIOLOGIC activators of apoptosis induction (5)?
    • intrinsic and extrinsic pathway inducers:
    • • intrinsic = growth factor withdrawal, survival factor withdrawal, glucocorticoids
    • • extrinsic = TNF-alpha, FasL
  38. What are DAMAGE-RELATED activators of apoptosis induction (5)?
    viral infection, heat shock, toxins, tumor suppressors, oxidants/free radicals
  39. What are THERAPY-ASSOCIATED activators of apoptosis induction (2)?
    UV/gamma radiation, chemotherapeutic drugs
  40. What are the intrinsic pathway inducers of apoptosis?
    • •growth factor withdrawal
    • •survival factor withdrawal
    • •glucocorticoids
    • -intrinsic often called mitochondrial pathway
  41. How does the intrinsic pathway work?
    • • upon mild ischemia, removal of nutrients, there is a withdrawal of growth factors (& the like)
    • • when apoptosis signal is received, pro-apoptotic Bcl-2 proteins (eg. BAD) are DEphosphorylated
    • • they bind to others on the outer mitochondrial membrane
    • • this results in loss of mitochondria membrane channel control and cytochrome C is released
    • • helps cleave caspase 9 --> begins caspase amplification
  42. What are extrinsic pathway inducers of apoptosis?
    • •TNF-alpha
    • •FasL (Fas ligand)
  43. How does the extrinsic pathway work?
    • • via receptor mediated apoptosis
    • • 2 death receptors may be expressed on a cell's membrane: TNF-alpha & FasL (fas ligand system, or FasL receptor)
    • -almost all cells have TNF-alpha receptors in their membrane
    • • a cell presenting a ligand will live
    • • cells with receptors will DIE
    • • once bound the receptor's death domain is activated and initiates caspase cascade
  44. Bcl
    both pro- and anti-apoptotic family of proteins
  45. Burkitt's Lymphoma
    • clinical correlate: apoptosis modulation, BcL proteins
    • •individual produces LOTS of pro-life Bcl proteins (eg. Bcl-2, Bcl-X1) but low levels apoptosis-inducing Bcl proteins (eg. BAD)
    • •results in excessive overgrowth of cells
  46. What activates the caspase pathway in the intrinsic & extrinsic pathways of apoptosis induction?
    • • intrinsic: Bcl protein dephosphorylation, complexing, and openings of mitrochondrial membrane channels to release cytochrome C
    • • extrinsic: binding of a TNF-alpha or FasL ligand to their respective receptors
  47. What are two differences and one similarity between the extrinsic and intrinsic pathways?
    • 1) intrinsic pathway is activated by: growth factor/survival factor withdrawal, glucocorticoids, viruses, DNA damage-causing events, toxins, oxidized compounds (free radicals), and ischemia
    • • extrinsic pathway is activated by TNF-alpha or Fas ligand binding to their receptors on the cell surface
    • 2) intrinsic, NOT the extrinsic pathway, can be modulated by the Bcl family proteins
    • 3) similarity: both pathways result in massive amounts of caspase-3 activity --> the chief executioner of cells undergoing apoptosis
  48. caspase 3
    cleaves cytoskeletal fibers and activates specific endonuclease that makes the ladder; common enzyme in apoptosis cascade
  49. How do the eye and testes confer immunological privilege?
    • • via the EXTRINSIC pathway
    • • all T-cells have Fas RECEPTORS on their surface
    • • blood vessels lining immune privileged sites constitutively express Fas-LIGAND on their endothelial cells
    • • when T-cells enter blood vessels lining privileged sites, Fas receptor on T-cells interacts with Fas-Ligand on endothelial cells
    • • T cells are induced to undergo apoptosis
  50. Hashimoto Disease
    HYPOthyroidism: apoptosis of thyroid cells leads to compromised thyroid function
  51. Dysregulated apoptosis is the hallmark of which conditions?
    • • Syndactyly + polydactyly
    • • cancers expansion
    • • cachexia (“wasting”) seen in some late-stage cancer patients
    • • Polycystic Kidney Disease
    • • Hashimoto’s (autoimmune form of hypothyroidism)
  52. Stroke
    • • clinical correlate: anti-apoptosis drugs
    • • inhibitors of apoptosis (IAPs) exist in humans; neuronal IAP can protect stroke victims from excessive loss of neurons if given in time
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Card Set
Cell Bio Apop/Cell Cycle (6)
Description
MBS Exam 1
Updated
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