Your SlideShare is downloading. ×
0
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Mechanism cell deaths
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×
Saving this for later? Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime – even offline.
Text the download link to your phone
Standard text messaging rates apply

Mechanism cell deaths

338

Published on

Published in: Technology
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
338
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
37
Comments
0
Likes
1
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. MECHANISMS OF CELL DEATH ISHAK MAT, PhD Translational Research Network Centre, Institut Perubatan dan Pergigian Termaju
  • 2. MECHANISMS OF CELL DEATH The mechanisms of cell death and cell survival are complex
  • 3. The mechanisms of cell death and cell survival are complex previously apoptosis necrosis
  • 4. apoptosis Due to the activation of a cascade of biochemical reaction resulting in cell death “Cell suicide” necrosis
  • 5. apoptosis Due to the activation of a cascade of biochemical reaction resulting in cell death “Cell suicide” necrosis Due to adverse conditions in the cell environment, causing acute injury leading to “biological accident” “Death by injury”
  • 6. apoptosis Cells are induced to commit suicide “Cell suicide” necrosis -mechanical damage -exposure to toxic chemicals “Death by injury”
  • 7. apoptosis Cell changes: 1. Formation of small blebs 2. Breakdown of nucleus 3. DNA fragmentation 4. Blebs contain cellular organelles 5. The cells break into several apoptotic bodies with organelles 6. The organelles within the apoptotic bodies are still functional 7. No tissue damage
  • 8. apoptosis -approximately 50 to 70 billion cells die each day due to apoptosis in a normal human being -In a year, this amounts to the proliferation and subsequent destruction of a mass of cells equal to an individual's body weight.
  • 9. necrosis Cell Processes: 1. Formation of small blebs 2. Changes in nuclear structure 3. The various blebs fused and become larger 4. No organelles in the blebs 5. Rupture of cell membrane, releasing content of cells 6. Organelles are non-functional 7. Induction of inflammation 8. Tissue damage
  • 10. Normal cell Small blebs Small blebs Big blebs,no organelles DNA fragmentat ion, organelles in the blebs Cell membrane ruptures, organelles non functional necrosis Inflammation of surrounding tissues apoptosis Apoptotic bodies, organelles functional, no inflammation
  • 11. Why commit suicide (apoptosis)? 1. Needed for proper development to take place, eg - resorption of the tadpole tails in its metamorphosis into a frog occur via apoptosis - The formation of the fingers and toes of the fetus occur via apoptosis of the tissue between them. - Sloughing of the inner lining of the uterus at the start of menstruation. - Formation of proper synapses requires apoptosis of excess neuron
  • 12. Why commit suicide (apoptosis)? 2. To destroy cells threatening the integrity of the organisms. e.g Cells infected with viruses are killed by cytotoxic T lymphocytes by apoptosis e.g via Fas-Fas ligand interaction A receptor called CD95 [Fas] on virus infected cell
  • 13. Why commit suicide (apoptosis)? 2. To destroy cells threatening the integrity of the organisms. e.g Cells infected with viruses are killed by cytotoxic T lymphocytes by apoptosis e.g via Fas-Fas ligand interaction A receptor called CD95 [Fas] on virus infected cell Tc Fasligand on Tc Fas-Fas-ligand binding induces apotosis of virusinfected cells
  • 14. Why commit suicide (apoptosis)?
  • 15. Why commit suicide (apoptosis)? 2. To destroy cells threatening the integrity of the organisms. e.g Winding down of Effector T cells once the immune response has been completed. Teff Self induced apoptosis Each other Teff
  • 16. Why commit suicide (apoptosis)? 2. To destroy cells threatening the integrity of the organisms. e.g Winding down of Effector T cells once the immune response has been completed. Teff Self induced apoptosis Each other Success: no self destruct Teff Failure: autoimmune diseases [eg SLE, rhematoid arthritis]
  • 17. Why commit suicide (apoptosis)? 3. Cells with DNA damage Can lead to: i. Distruption of proper development leading to birth defect ii. Formation of cancer DNA damage Increase production of normal p53 molecule Potent inducer of apoptosis Mutation of p53 Cell suicide/death Increase cancer incidence
  • 18. Why commit suicide (apoptosis)? 4. Radiation and Chemotherapy - have been shown to lead to apoptosis in some types of cancer
  • 19. What makes a cell to undergo apoptosis?
  • 20. What induces apoptosis? Withdrawal of positive signals: eg Receipt of negative signals: -Growth factors for neuron -increase levels of oxidants -Interleukin-2 for lymphocytes -DNA damage [UV, X-ray, chemo] -molecules that induce apoptosis
  • 21. What induces apoptosis? Withdrawal of positive signals: eg -Growth factors for neuron -Interleukin-2 for lymphocytes Receipt of negative signals: -molecules that induce apoptosis Tumour necrosis factor-alpha (TNFalpha) TNFR TNFbeta TNFR FasL Bind to cell surface Fas
  • 22. Mechanisms of apoptosis? 1. The internal or intrinsic pathways 2. External molecules binding to cell surface receptors. 3. Due to reactive oxygen species
  • 23. Mechanisms of apoptosis? 1. The internal or intrinsic pathways Healthy cell Mitochondria Bcl-2 displayed on the outer membrane of mitochondria Inhibits apoptosis
  • 24. Mechanisms of apoptosis? 1. The internal or intrinsic pathways Internal damage to healthy cell Mitochondria Bax protein, a related molecules Migrates to the surface and inhibits the protective effects of Bcl-2 Bcl-2
  • 25. Mechanisms of apoptosis? 1. The internal or intrinsic pathways Internal damage to healthy cell Mitochondria Bax protein, a related molecules Insert itself to the outer mitochondrial membranes and punch holes Bcl-2
  • 26. Mechanisms of apoptosis? 1. The internal or intrinsic pathways Internal damage to healthy cell Mitochondria Bcl-2 Leaking of cytochrome c Apoptosomes bind to and activate caspase 9 enzymes Binds to apoptotic protease activating factor1 (Apaf-1) The complexes aggregate to form apoptosomes
  • 27. Mechanisms of apoptosis? 1. The internal or intrinsic pathways Internal damage to healthy cell Mitochondria There are about a dozen of caspases enzymes - all proteases Apoptosomes bind to and activate caspase 9 enzymes Bcl-2 Cleaves and activates other enzyme [caspase 3 and 7]
  • 28. Mechanisms of apoptosis? 1. The internal or intrinsic pathways Cleaves and activates other enzyme [caspase 3 and 7] Internal damage to healthy cell Expanding activation of proteolytic enzymes leading to: Digestion of structural proteins in the cytoplasm Degradation of chromosomal DNA Phagocytosis of the cell
  • 29. Mechanisms of apoptosis? 2. Induction by external signal Fas TNFR
  • 30. Mechanisms of apoptosis? 2. Induction by external signal Fas FasL TNF TNFR
  • 31. Mechanisms of apoptosis? 2. Induction by external signal Fas Transmit signal to the cytoplasms FasL [on cells] TNF Activate caspase 8 Leading to destruction and phagocytosis TNFR
  • 32. Mechanisms of apoptosis? 3. Apoptosis-inducing factor AIF) Neuron - self destruct without using caspases Induction of cell death When the neuron receives signal to die Trigger the destruction of the DNA AIF is released from the mitochondria Migrate to the nucleus and bind to DNA
  • 33. Mechanisms of Necrosis? Necrotic Cell Death 1. Loss of metabolic functions 2. Loss of the integrity of the cell membranes 3. Cessation of the production of proteins and ATP. 4. Cells organelles swell and become nonfunctional.
  • 34. Mechanisms of Necrosis? 1. Depletion of ATP-leads to breakdown of the cell’s ion balance 2. Reduce oxygen level (hypoxia) 3. Oxidative stress - the presence of excess oxygen radicals
  • 35. Other mechanisms of cell death and cell survival: 3. Autophagy 4. Post-Mitotic Death 5. Entosis
  • 36. Other mechanisms of cell death and cell survival: 3. Autophagy In cell biology, autophagy, or autophagocytosis, is a catabolic process involving the degradation of a cell's own components through the lysosomal machinery.
  • 37. Other mechanisms of cell death and cell survival: 3. Autophagy -a tightly regulated process -help maintain a balance between the synthesis, degradation and subsequent recycling of cellular products
  • 38. Other mechanisms of cell death and cell survival: 3. Autophagy: the main mechanisms - formation of a membrane around the targeted region of a cell -followed by fusion of the vesicle with lysosome -subsequent degradation of the contents
  • 39. Other mechanisms of cell death and cell survival: 5. Entosis
  • 40. ENTOSIS • Scientists have discovered a novel form of cell death in which cells crawl inside other cells to die. • The process, dubbed entosis, may be a method of suppressing tumors, the researchers say, but others aren't so sure.
  • 41. ENTOSIS • http://www.youtube.com/watch? v=Zp61OzvKRHY

×