APOPTOSIS

Apoptosis pathways

1. Prepared by ASHISH R. CHAUDHARI (M.Pharm) 03-03-2021 1 APOPTOSIS

2. INTRODUCTION Apoptosis is the process of programmed cell death. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation. Between 50 and 70 billion cells die each day due to apoptosis in the average human adult. For an average child between the ages of 8 and 14, approximately 20 billion to 30 billion cells die a day. 03-03-2021 2

3. Each living organism has its own life spam and this pattern is followed by each organ or an organism. During the development of organ or organism, there is selective, patterned death of several cell occur. This is called as Apoptosis or programmed cell death. Apoptosis is generally controlled programed cell death, basically involved in developmental process and immune defense system of an organism. Apoptosis can be triggered by various internal (intrinsic) and external (extrinsic) signals. APOPTOSIS 03-03-2021 3

4. HISTORY OF APOPTOSIS German scientist Carl Vogt was first to describe the principle of apoptosis in 1842. Fleming 1885 studied the similar phenomenon in epithelial cells and named as chromolysis. In 1972 Kerr first introduced the term apoptosis in a publication. Kerr received the Paul Ehrlich and Ludwig Darmstaedter Prize on March 14, 2000, for his description of apoptosis. The 2002 Nobel Prize in Medicine was awarded to Sydney Brenner, Horvitz and John E. Sulston for their work identifying genes that control apoptosis. 03-03-2021 4

5. Thus Apoptosis can also be defined as the genetically controlled structural and functional death of a cell. The cell death may occur in two different ways Death by Injury If there is any mechanical damage to the integrity of cell which is unrepairable, in such case the cell death occurs. Death by suicide By cell shrinkage (due to insufficient food and nutrition) By development of bubble like blooms on cell of surface Chromatin degradation By mitochondrial breakdown [after the mitochondrial breakdown, it release Cytochrome-C and Reactive Oxygen Species (ROS) which are toxic to cell protoplasm]. 03-03-2021 5

6. CASPASE Caspase are the family of protease enzymes playing essential role in programmed cell death. 03-03-2021 6 It is family of cystein protease. P resent in cell in inactive form. Cleave protein bearing a amino acid sequence located at the terminal.

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8. 03-03-2021 8 BIOCHEMICAL CHANGES RELATED WITH APOPTOSIS Following changes can be observed in Apoptosis Chromatin condensation and degradation Fragmentation of DNA Formation of Apoptotic bodies These are supposed to be biochemical characters of Apoptosis. These changes during Apoptosis occurs due to action of DNAses and Proteases, which are present in nucleus or released by cell organelles. For example:- ICE protease family. Mitochondria also play an important role in Apoptosis. After infection by any pathogen to the cell at the site of invasion accumulate high level of toxic phenolic compound called as phytoalexins

9. 03-03-2021 9 MORPHOLOGICAL CHANGES IN APOPTOSIS

10. 03-03-2021 10 PATHWAYS TO APOPTOSIS 1) Death receptor pathways /(Extrinsic Pathway) 2) Mitochondrial pathways /(Intrinsic Pathway)

11. 03-03-2021 11 Death receptor pathways /(Extrinsic Pathway) Induction is mediated through cell surface receptors know to be ‘Death receptors’. Death ligands are activating these receptors. Further activation of Caspases leads to cell death

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13. 03-03-2021 13 Mitochondrial pathways /(Intrinsic Pathway) Release of protein from mitochondrial inner membrane into cytosol. DNA damage induce apoptosis. Cellular stress, heat shock, oxidative stress, cellular damage, that are also induced apoptosis.

14. 03-03-2021 14 INTRINSIC PATHWAY

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16. 03-03-2021 16 OVERALL GENETICS OF APOPTOSIS (PCD) It can be summarized in following four steps 1. Stimulation The extracellular signals recognized by receptors present on plasma membrane(CD45) 2. The Intracellular response The signal-Receptor complex (TNF/Fas-CD45) induce the intracellular signalling. It activates the transcription factor to induce Apoptosis related genes. 3. Cell dismantling The caspase cascade execution leads to the chromatin condensation and DNA degradation & expression of phagocyte recognition molecules. 4. Phagocytosis The phagocyte recognizing molecule recognize the degraded material in cell & binds with them to discard out of cell.

17. 03-03-2021 17 IMPORTANCE OF APOPTOSIS IN PLANTS Role in Xylogenesis Role in sex determination Role in Senescence and fruit ripening Role in plant defence Role in other ubiquitous plant processes

18. 03-03-2021 18 THANK YOU !