APOPTOSIS Vivek Giri Msc . Microbiology Semester- 1 P.G. Department Of Biosciences Sardar Patel University
Contents What is apoptosis ? Need for apoptosis Reasons for apoptosis Morphological changes during Apoptosis Apoptosis vs necrosis Caspases Pathways for apoptosis Bcl 2 protein Inhibitors of apoptosis (IAPs) Regulation of apoptosis Biochemical features of apoptosis Apoptosis gone wrong
What is Apoptosis? Apoptosis or Programmed cell death is an energy dependent naturally occuring process which helps the cell to destroy itself in response to appropriate signals In 1972, John F. Kerr, Andrew H. Wyllie and A. R. Currie, coined the term “apoptosis ” Apoptosis is a Greek name describing falling of leaves Study of the development of the nematode Caenorhabditis elegans by H. Robert Horvitz The average human loses 50 to 70 billions of cell every day due to apoptosis
Reasons for apoptosis
Morphological changes during Apoptosis Apoptosis of T Lymphocytes in Systemic Sclerosis - Scientific Figure on ResearchGate . Available from: https://www.researchgate.net/figure/Morphological-cell-changes-during-apoptosis-42_fig1_221923701 [accessed 16 Aug, 2022]
Cell death
Apoptosis Necrosis Morphological changes Membrane blebbing with loss of membrane integrity Loss of membrane integrity Aggregation and margination of chromatin Random fragmentation of chromatin Cellular shrinkage Cellular swelling Formation of apoptotic bodies Cell lysis Persistence of apoptotic bodies Swelling and disintegration of organelles Biochemical changes Genetically controlled activation of enzymes Loss of ion homeostasis ATP-dependent process Passive process (no energy requirement) Generation of non-random oligonucleosomes of DNA (ladder pattern on agarose gel) Random digestion of DNA (DNA smear on agarose gel) Early pre- lytic DNA fragmentation Late post-lytic DNA fragmentation Physiological significance Death of individual or small groups of cells Death of large contiguous groups of cells or organ segments Evoked by physiological stimuli Evoked by pathological stimuli Phagocytosis by macrophages or neighboring cells Phagocytosis by macrophages No inflammation Acute inflammation
The Role of GnRH Analogues in Endometriosis-Associated Apoptosis and Angiogenesis - Scientific Figure on ResearchGate . Available from: https://www.researchgate.net/figure/Comparison-of-the-cellular-changes-that-occur-during-apoptosis-and-necrosis_fig1_51434475 [accessed Aug 20, 2022]
Activation of caspases
Pathways for Apoptosis
Extrinsic pathway
Regulation of extrinsic pathway Apoptosis in Cancer: Key Molecular Signaling Pathways and Therapy Targets - Scientific Figure on ResearchGate . Available from: https://www.researchgate.net/figure/The-extrinsic-pathway-of-apoptosis-and-its-regulation-Death-receptor-signaling-can-be_fig3_26280189 [accessed 18 Aug, 2022]
Intrinsic Pathway
Assembly of the mammalian apoptosome
Intrinsic pathway of apoptosis
The role of pro-apoptotic effector Bcl2 family proteins (mainly Bax and Bak ) in the release of mitochondrial intermembrane proteins in the intrinsic pathway of apoptosis. When activated by an apoptotic stimulus, the effector Bcl2 family proteins aggregate on the outer mitochondrial membrane and release cytochrome c and other proteins from the intermembrane space into the cytosol by an unknown mechanism
How pro-apoptotic BH3-only and anti-apoptotic Bcl2 family proteins regulate the intrinsic pathway of apoptosis.
Dai, Yao et al. “Overcoming cancer therapy resistance by targeting inhibitors of apoptosis proteins and nuclear factor-kappa B.” American journal of translational research vol. 1,1 (2009): 1-15.
Regulation of Apoptosis Proposed intracellular pathways leading tocell death by apoptosis or to trophic factor-mediated cell survival in mammalian cells. [ Adapted from B Pettman and C E Henderson,1998, Neuron 20:633 l