Apoptosis, program cell death

Introduction
Definition
History
Evolution and origin of apoptosis
Significance
Purpose of apoptosis
Steps /process
Morphological and biochemical changes
Mechanism of apoptosis
Caspases
Regulation of apoptosis
Disorders of apoptosis
Application
Conclusion
Referances

1. APOPTOSIS By KAUSHAL KUMAR SAHU Assistant Professor (Ad Hoc) Department of Biotechnology Govt. Digvijay Autonomous P. G. College Raj-Nandgaon ( C. G. )

2. Contents Introduction Definition History Evolution and origin of apoptosis Significance Purpose of apoptosis Steps /process Morphological and biochemical changes Mechanism of apoptosis Caspases Regulation of apoptosis Disorders of apoptosis Application Conclusion Referances

3. INTRODUCTION The word apoptosis comes from the ancient Greek meaning the; “ Falling of petals from a flower or of leaves from a tree in autumn” Apoptosis is the process of programmed cell death. Biochemical events lead to characterisitic cell changes include, cell shrinking, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation. Between 50-70 billion cells die each day due to apoptosis in the average human adult. For an average child between the ages of 8-14, approximately 20 billion to 20 billion cells die a day.

4. HISTORY German scientist Carl Vogt was first to describe the principle of apoptosis in 1842. 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.

5. Definition A pathway of cell death induced by a tightly regulated suicidal program , in which the cells destined to die activate enzymes that degrade cells own nuclear DNA and cytoplasmic protein. It is programed by genetics protocol of program (control of enzyme, cell membrane, cytoplasmic molecules, signal transduction ) etc..

6. Evolution of the origin of programmed cell death Mitochondria retain their collection of molecules that can trigger cell suicide after they enter and stabilize in the eukaryotic cell. This process has evolved to occur only when programmed.

7. SIGNIFICANCE In the human body about 100,000 c ells are produced every second by mitosis and a similar number die by apoptosis(Vaux and Korsmeyer , 1999,Cell). 1] Development & morphology Massive cell death occurs during early development of the nervous system (> 50percent of all neurons die) 2] Homeostasis 3] Deletion of damaged and dangerous cells

8. Purpose of apoptosis why should a cell commit suicide It’s essential for the proper development and to maintain homeostasis for the organism. Apoptosis is needed for proper development; The resorption of the tadpole tail. The formation of the fingers and toes of the fetus. The sloughing off of the inner lining of the uterus. The formation of the proper connection between neurons in the brain. Apoptosis is needed for self defance Cells infected with viruses Cells of the immune system cells with DNA damage Cancer cells

9. STEPS Apoptosis consists of 4 steps: the decision to activate the pathway; the actually "suicide" of the cell; engulfment of the cell remains by specialized immune cells called phagocytes; degradation of engulfed cell. The actual steps in cell death require: condensing of the cell nucleus and breaking it into pieces condensing and fragmenting of cytoplasm into membrane bound apoptotic bodies; and breaking chromosomes into fragments containing multiple number of nucleosomes (a nucleosome ladder)

10. Morphological and biochemical changes Classic change Biochemical changes Cell shrinkage Nuclear fragmentation Chromatin condensation Chromosomal DNA fragmentation Formation of cytoplasmic blebs and apoptosis bodies Phagocytosis Activation of caspases Protolysis of cytoskeletal protein Cross linkage of protein molecules Fragmentation of nuclear chromatin by activation of nuclease. Membrane alteration and recognition by phagocytosis .

11. Mechanism of apoptosis extrinsic pathway- cytochrome c caspases cell death. A] External signalling pathway Apoptosis is triggered by external (extracellular) stimulus. Also known as Receptor mediated apoptosis

12. 2] Intrinsic signalling pathway Intrensic pathway- death receptor caspases cell death. Also called as mitochondria mediated pathway.

13. Caspases - the initiator & executioner of apoptosis There are 14 mammalian caspases identified to date. The term caspases is derived from c ysteine -dependent asp artate -specific prote ases Caspases subdivided into 3 functional groups : 1. initiator caspases - ( caspases 2,8,9,10) 2. executioner caspases ( caspases 3,6,7) 3. inflammatory caspases (1,4,5,11,12) Single chain of pro enzymes. Contains an N-terminal domain, a small subunit and a large subunit (similar to a ribosome). Apoptosis stimulus activation substrate cleavage enzyme. Some common targets

14. Regulation of apoptosis Regulatory protein – BCL-2 , equivalent to CED-9 Apoptosis depends on binding of BCL-2 with pro apoptotic and anti apoptotic proteins. Situated in the outer mitochondrial membrane. Apaf-1 equivalent to CED-4.

15. Disorder of apoptosis TOO MUCH- tissue atrophy Neurodegeneration , thin skin etc. TOO LITTLE- hyperplasia cancer, athersclerosis etc. Apoptosis inhibition Neoplastic disease Autoimmunity [ e.g. systemic lupus erythematosus ] Viral infection Hyperactive apoptosis Neurodegenerative disease

16. Importance of apoptosis 1. Crucial for embryonic development ; Errors in apoptosis can lead birth defects. 2. Importance for maintaining homeostasis ; - Cell death is balanced with mitosis to regulate cell number. 3. Apoptosis helps eliminates cells that are injured ; Such injured cells include; A) cells with damaged DNA. B) cells with misfolded proteins C) cells suffering from certain infections etc. 4. Important in normal physiology/development DEVELOPMENT; immune systems maturation, morphogenesis, neural development. Adult ; immune privilege, DNA damage and wound repair.

17. Conclusion Apoptosis play a significant role in survival by maintaining homoeostasis in multicellular organisms and the management of many diseases. Evidence show that malfunctioning of apoptosis pathway may cause several human diseases like cancer, neurodegenerative as well as several type of autoimmune disorder.

18. References BOOKS The Cell- A molecular approach 4 th edition- G.M. Cooper & R.E. Hausman Cell and molecular biology 6 th edition- Gerald Karp.   Articles   Apoptosis—an introduction by Alfons Lawen 25:888–896, 2003. Apoptosis – reprogramming cell fate. Hoi Hung Cheung et al- Volume 2012, Article ID 685852, 8 pages. Apoptosis and disease - R. Ramírez Chamond et al - Vol. 14, No. 6, pp. 367-374 Introduction to Apoptosis - by Andreas Gewies in 2003, pp. 1-26