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4.12.2010
4.12.2010
4.12.2010
4.12.2010
4.12.2010
4.12.2010
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4.12.2010

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  • 1. 4.12.2010<br />
    • Types of Pathways for Cell death
    • 2. Extrinsic
    • 3. Fas/Fas Ligand Pathway aka “Death Receptor”
    • 4. Links procaspases to Fas/FasL receptor complex by FADD
    • 5. Activated caspase 8 cleaves caspase 3
    • 6. Apoptosis activated
    • 7. Activates endonucleases
    • 8. Enzymes that cut DNA in between nucleosomes (internucleosomal cleavage – a sign of apoptosis)
    • 9. Organization of apoptotis is why endonucleases are used in a specific way to cleave the DNA
    • 10. Activates proteases
    • 11. Cleaves nuclear and cytoplasmic/skeletal proteins
    • 12. Drives assembly/formation of apoptotic body
    • 13. Allows phagocytic cells to come in and engulf the dying cell without inducing inflammation
    • 14. Perforin and Granzyme – used primarily in the immune system.
    • 15. Cytotoxic cells, which are immune cells, target a cell for death by releasing perforin through exocytosis
    • 16. Perforin perforates membrane and forms a pore
    • 17. Allows for granzyme to be inserted through pore
    • 18. Activates caspase 3
    • 19. Work like endonucleases too to cleave DNA directly
    • 20. Perferin has hydrophobic/hydrophilic region, ampipathic, inserts in membrane, conof change and cell death ensues through granzyme
    • 21. Cytotoxic cells sense viral infections, bacterial infections, and neoplastic change, or becoming oncogenic
    • 22. Surivial Mode
    • 23. Bcl2 is more prominent as well as anti-apoptotic proteins
    • 24. Caspase 12 comes from ER
    • 25. Turned on by stress sensors
    • 26. Enzymes that can cleave procaspase 12 in ER and release to activate caspase 3
    • 27. These stress proteins (IREs) are activated that sense the cell has a buildup of misfolded proteins (IREs sense the buildup of misfolded proteins – they sense the stress of the misfolded proteins building up in the ER, the family of proteins then activates caspase 12)
    • 28. Cleave caspase 12, activating it, from procaspase (pro section cleaved off by IREs)
    • 29. Activates caspase 3
    • 30. Apoptosis
    • 31. Way for tissue to eliminate cell that don’t produce the right proteins that aren’t making a good cell
    • 32. ER stress sensors – IRE’s that activate caspase 12
    • 33. IAP – inhibitors of apoptosis
    • 34. We used to think that apoptosis was an all or nothing thing, but the identification of IAPs provided an understanding of ways the cell can regulate apoptosis
    • 35. Can stop apoptosis at any stage because they directly interact with activated caspases anywhere along the way.
    • 36. 70 amino acid sequence Baculovirus Sequence.
    • 37. A BIR
    • 38. Bacular Virus Internal Repeat
    • 39. Common to all inhibitors of apoptosis
    • 40. Highly conserved
    • 41. Identified in baculoviruses first
    • 42. Conservative – so very important
    • 43. Allows interacting area with caspases
    • 44. Allows to interact directly with caspases or complexes that lead to caspase 3 activation.
    • 45. Suppress apoptosis
    • 46. Protein complexes from the mitochondria breaking down inhibit IAPs
    • 47. Intrinsic Signals
    • 48. Withdrawal of trophic factors
    • 49. P53
    • 50. Bax destabilizes cell membrane and releases cytochrome c
    • 51. Apf-1 and cytochrome c come together to cleave procaspase 9, makes an apotosome
    • 52. Activates caspase 3 from procaspase 3
    • 53. Activates endonuclease activity, which cleave DNA, for apoptosis between nucleosomes
    • 54. Proteases are activated, which degrade nuclear and cytoskeletal proteins
    • 55. Cytoskeleton remodeling
    • 56. Responsible for formation of apoptotic bodies/ “blebs”
    • 57. Phagocytose, chew up, some spit out and used by endocytosis or pinocytosis and used to remake organelles etc or other components
    • 58. Other forms of Cell Death
    • 59. Aponecrosis
    • 60. A combination of apoptosis and necrosis
    • 61. Cell death induced by injury, much like necrosis
    • 62. Has a phenotype of necrosis
    • 63. But involves protein synthesis like apoptosis
    • 64. We don’t know why
    • 65. Requires gene transcription like apoptosis
    • 66. Autophagy
    • 67. Removes dead or dying organelles to the lysosomes and uses them for metabolic purposes
    • 68. Can involve formation of an autophagosome
    • 69. ER membrane surrounds organelles to make autophagosomes
    • 70. fuses with lysosomes to make an autophagolysosome
    • 71. breakdown entire cell substituent
    • 72. Cell may want to replace and use the components for ATP or generation of other things
    • 73. If the environment is not sufficient, not enough nutrients or GFs, the cell may breakdown organelle membranes inside the cell and use that for ATP
    • 74. Not enough oxygen, then may break down – oxidative stress
    • 75. Some type of cell death
    • 76. Radiation
    • 77. Chemotherapy
    • 78. Trigger autophagy where all internal contents are degraded.
    • 79. Intracellular pathogens
    • 80. Cells infected, without increasing chance of infecting neighbors, eliminates intracellular infection internally
    • 81. TB
    • 82. Viral infection
    • 83. Lack of growth factors or nutrients in environment
    • 84. Other cells need materials to make glucose or ATP
    • 85. Use substituents of other cells to make ATP such as phospholipids etc.
    • 86. Cannibalism is in our nature!
    • 87. Characteristics
    • 88. Autophagian vacuoles form
    • 89. Nucleus is left fairly in tact
    • 90. Chromsomes will not undergo condensation/cleave such as in apoptosis
    • 91. Can be used to provide a source of materials for neighboring cells
    • 92. Huntington’s/Alzheimers Disease
    • 93. Benefits
    • 94. Removal of damaged organelles
    • 95. Limitation of infection
    • 96. Use components of organelles for metabolic substrates
    • 97. How it works
    • 98. Membrane surround Organelle from ER to form autophagosome
    • 99. Fuses with lysosome to make autophagolysosome
    • 100. Parapoptosis
    • 101. Apoptotic-like form of cell death, but uses an alternate form of caspase 9, cytochrome c
    • 102. Alternative form of cell death driven by formation of apotosome like structure
    • 103. Cytochrome c release + activation of caspase 9
    • 104. This alternate form does NOT use APAF-1
    • 105. Many inhibitors that block apotosomes do not affect this form of cell death (first identified this way)
    • 106. Can be induced by internal or external factors
    • 107. External, lack of GF’s outside of cell
    • 108. Seen in Huntington’s Disease/Alzheimer’s Disease/ALS (Amyotrophic lateral sclerosis aka Lou Gehrig’s Disease)
    • 109. Involved in activation of caspase 9 but no formation of apotosomes
    • 110. It is not inhibited by the caspase 3 inhibitor, so we can’t block it like we could in normal apoptosis
    • 111. Involves cytoplasmic indulution
    • 112. Vacuoles form
    • 113. Degrade contents of the cytoplasm
    • 114. Mediated by MAP kinase pathway
    • 115. Leads to activation of caspase 9 and cell death
    • 116. Triggered by immune cell death signaling molecules that target cells for death
    • 117. Tumor necrosis factor
    • 118. Bound by TNF receptor
    • 119. Triggers cells death
    • 120. Usually mediated by caspase 9
    • 121. Primarily activates other signaling molecules aside from MAP kinase
    • 122. Caspase 3 independent
    • 123. If cell is released and into the lumen, two types of cell death can occur
    • 124. Used primarily for metastatic cells
    • 125. Anoikis
    • 126. Form of apoptosis that ensues after cell is detached from ECM
    • 127. Activation of caspases
    • 128. Release of cytochrome c
    • 129. Death when cells become detached from ECM
    • 130. ECM is a substrate to which cells adhere to organize and form tissue
    • 131. If a cell, like epithelial, becomes detached
    • 132. ‘loss of home’
    • 133. TJ and AJ – adherin junction and tight junctions
    • 134. Hold cells to one another
    • 135. Integrin attachments hold cell to ECM
    • 136. All attachments have been degraded
    • 137. When cells detach, they are unhealthy of neoplastic, tumoregenic
    • 138. Released from normal environment
    • 139. Entosis
    • 140. Not a type of cell death that involves apoptotic mechanisms
    • 141. 2 cells detach from ECM and go to lumen of tissue, but remain attached to one another at only one site
    • 142. one sucks up the other and brings it into the cytoplasm to form into a vacuole called an entocyte
    • 143. can spit out…
    • 144. autophagic-like mechanism begins to degrade the entocyte
    • 145. Identified in mammals/ breast cancer tissue
    • 146. May be a way to degrade neoplastic cells in cancer
    • 147. Cells that are lucent, become sucked up by neighboring cells
    • 148. Engulfed like phagocytosis
    • 149. The loosening of the cell
    • 150. Degrades entire cell
    • 151. Think It is a likely way of preventing oncogenic cells
    • 152. Neoplastic
    • 153. A cell is demonstrating features of cancer, or being cancerous.
    • 154. End Lecture----------------------------------------------------------------------------------------
    • 155. --------------------------------The Extracellular Matrix------------------------------------------------
    • 156. Disease linked to abnormalities in the ECM
    • 157. Cancer
    • 158. Osteoporosis
    • 159. Osteoarthritis
    • 160. Inflammatory Diseases
    • 161. Periodontal Disease
    • 162. Neurodegenerative Diseases
    • 163. Tissues
    • 164. Muscular tissues
    • 165. ECM is usually between cells, a thin layer surrounding plasma cell membrane (basal lamina refers to thin ECM material that surrounds plasma membrane, instead of ECX. Epithelial, thin layer below ECM directly below skin)
    • 166. Smooth
    • 167. Cardiac
    • 168. skeletal
    • 169. Nervous tissue
    • 170. Central NS
    • 171. Peripheral NS
    • 172. ***Connective tissue (focus of time in this section)
    • 173. Bone
    • 174. Osteocytes sit in bone and secrete calcified ECM that makes bone tissue or have blood run through
    • 175. Cartilage
    • 176. Less dense than bone
    • 177. Cells secrete components of cartilage and ECM components of it
    • 178. Loose connective tissue
    • 179. Under epithelial cells
    • 180. Less dense than cartilage
    • 181. Form strands in gel like substance
    • 182. Immune cells move through
    • 183. Blood vessels penetrate
    • 184. Under skin or intestinal lining
    • 185. ***Blood
    • 186. osteocytes secrete ECM molecules
    • 187. Immune cells
    • 188. ***Lymphoid tissue
    • 189. Basal Lamina
    • 190. The area attached to ECM
    • 191. Epithelial Cells
    • 192. Packed tightly to one another, held by TJ and AJ, linked up by integrins at the basal side of the cell and attach TO the basal lamina
    • 193. Lumen of Gut
    • 194. Epithelial cells
    • 195. Attached to basal lamina of ECM
    • 196. Adhere to loose connective tissue
    • 197. LCT
    • 198. Strand like
    • 199. Endothelial cells of lumen of blood vssesl
    • 200. Blood vessels allow immune cell transportation
    • 201. GAG’s
    • 202. Glycosylamino glycoproteins
    • 203. Allows for gel like substance to form
    • 204. Fibroblasts can stop making things to adhesion
    • 205. Endothelial cells of blood vessels, surrounded by smooth muscle cells.

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