PHRD5015 Mechanisms of Disease - Module 2 (Signaling in the Multicellular Environment)

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daynuhmay
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PHRD5015 Mechanisms of Disease - Module 2 (Signaling in the Multicellular Environment)
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2013-09-16 14:51:23
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Mechanisms Disease
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Mechanisms of Disease
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  1. G protein bound to 1 adrenergic receptors
    Gs
  2. G protein bound to 2-adrenergic receptors
    Gq
  3. activates PLC
    Gq
  4. hormone that increases cardiac myocyte contractility
    norepinephrine
  5. cleaves phosphatidyle inositol (PIP3)
    PLC
  6. DAG
    remainder of PIP3 in the membrane after cleavage
  7. ligand for Ca2+ channels on ER
    inositol triphosphate (IP3)
  8. activates PKC
    PLC
  9. localizes PKC to membrane
    DAG
  10. 2 requirements for PKC activation
    • 1) DAG
    • 2) Ca2+
  11. result of coupling 2 adrenergic receptors to Gi
    inhibition of adenylate cyclase
  12. P/S NS NT
    ACh
  13. P/S NS receptors
    muscarinic receptors
  14. G protein bound to mAChR
    Gq
  15. central regulator of smooth muscle tone
    Ca2+ levels
  16. sympathetic signal targets
    smooth muscle
  17. parasympathetic signal targets
    vascular epithelium
  18. mediates activation of NOS
    ACh
  19. eNOS activator
    calmodulin
  20. activates the production of vascular smooth muscle cGMP
    endothelial NO
  21. cGMP effect on smooth muscle cells
    promotes relaxation by opposing Ca2+
  22. 3 stages of angiogenesis
    • 1) initiation
    • 2) invasion
    • 3) maturation
  23. 2 regions of ECM
    • 1) basement membrane
    • 2) interstitial matrix
  24. proteins constituting basement membrane
    • type IV collagens
    • laminins
    • fibronectic
  25. proteins constituting interstitial matrix
    • fibrillar collagens
    • proteoglycans
    • glycoproteins
  26. link cell to ECM
    integrins
  27. activate focal adhesion kinase (FAK)
    integrins
  28. signal for the growth of new blood vessels
    hypoxia
  29. HIF-1
    TF induced in any cell in response to decreased O2
  30. prolyl hydroxylase (PHD)
    hydroxylates HIF-1 under normoxic conditions
  31. PHD cofactor
    O2
  32. activates VEGF transcription
    HIF1
  33. -primary receptor mediating angiogenesis
    -RTK consisting of 2 identical subunits
    VEGFR2
  34. angiogenesis mediating receptor that promotes the activation of PLC and PI3K
    VEGFR2
  35. how PKC activates MAPK cascade
    via Raf-1
  36. docking site for PKC
    DAG
  37. overexpresses VEGFR2 (and suppresses expression in surrounding cells)
    tip cell
  38. high expression of Hes, Hey, VEGFR1
    stalk cells
  39. membrane protein that serves as a ligand for Notch and cleaves it upon binding
    Dll4
  40. PI3K promoted VEC migration mechanism
    VEGFR2 activates PI3K -> P-Akt -> actin monomer polymerization
  41. respond to absolute concentration of VEGF (tip vs stalk)
    stalk cells
  42. cells that render the vascular tube VEGF independent & seal it
    pericytes
  43. condition in which new blood vessels are pericyte poor
    diabetic retinopathy
  44. secreted by pericytes
    TGF
  45. secreted enzymes that break down ECM components
    matrix metalloproteinases (MMPs)
  46. endogenous factor inhibiting angiogenesis
    fragments of collagen IV

    (bind & inhibit integrin signaling)
  47. H responsible for storing energy during times of feeding
    insulin
  48. H responsible for mobilizing energy during times of fasting
    glucagon
  49. insulin sensitive glucose transporter
    GLUT4
  50. rate limiting step in glucose storage and glucose utilization
    glucose uptake
  51. glucose is immediately converted to ____ upon uptake in cell
    glucose-6-phosphate
  52. substrate for insulin RTK
    IRS1 (insulin receptor substrate 1)
  53. docking site for PI3K via its SH2 domain
    phosphorylated site on IRS1
  54. pathway for PI3K promotion of vesicle fusion
    insulin -> p-insulin RTK -> p-IRS1 -> PI3K -> IP2 converted to IP3 -> PDK docks at IP3 -> p-Akt -> exocytosis of GLUT4 for surface deposition
  55. pathway for gluconeogenesis inhibition by insulin
    insulin -> p-Akt -> p-FOXO1 (p inhibits)
  56. -breaks down fat into FA and glycerol for uptake
    -stimulated by insulin
    LPL - lipoprotein lipase
  57. -breaks down triglycerides in adipocytes for use
    -inhibited by insulin
    HSL - hormone sensitive lipase
  58. glucagon/cAMP regulation
    glucagon -> glucagon receptor -> Gs -> AC -> cAMP -> active PKA
  59. 5 functions of Akt
    • 1) increase glycogen synthesis
    • 2) increase FA and triacyl glycerol synthesis
    • 3) decrease gluconeogenesis
    • 4) decrease lipolysis
    • 5) increase glucose transport
  60. insulin proliferation pathway
    insulin receptor -> Shc -> Grb/SOS -> Ras -> MAPK -> proliferation
  61. inhibits glycogen synthase
    glycogen synthase kinase
  62. AMPK activators (4)
    • 1) hypoxia
    • 2) ischemia
    • 3) heat shock
    • 4) exercise
  63. AMPK inhibits.. (3)
    • 1) adipose FA synthesis
    • 2) hepatic gluconeogenesis
    • 3) mTOR
  64. enzymes which modify other proteins
    sirtuins
  65. -enzyme that is a key metabolic sensor in tissues associated with metabolism regulation
    -NAD+ dependent
    SIRT1
  66. electron acceptor
    NAD+
  67. electron donor
    NADH
  68. energy deficit if NAD+ levels are ____
    high
  69. deacetylates FOXO1 and PGC1 to activate them
    SIRT1
  70. involved in gluconeogenesis enzyme transcription
    FOXO1
  71. involved in FA oxidation enzyme transcription
    PGC1

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