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Cell death- NECROSIS, APOPTOSIS Cell aging: Cellular changes during aging General mechanism of cyclin -CDK interaction Role of cyclins and cdks Cell cycle pathway of apoptosis Contents 3 Different reasons for occurring apoptosis Autophagy

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4 Introduction CELL CYCLE Definition The regular occurrence of different stages like G 1 , S, G 2 and Mitotic phase of the cell in a cyclic manner is called cell cycle. PHASES OF CELL CYCLE G 1 phase S phase or DNA synthesis phase G 2 phase Mitotic phase (M phase) INTERPHASE PROPHASE, METAPHASE ANAPHASE TELOPHASE

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ROLE OF CYCLINS AND CDKS Cyclin -dependent kinases (CDK) belong to a group of protein kinases involved in the regulation of the cell cycle . A cyclin -dependent kinase is activated by association with a cyclin , forming a cyclin -dependent kinase complex . Evans et al. 1983 discovered cyclins in sea urchin eggs and suggested the biochemical mechanism that drives the cell cycle Cyclin is a protein that contains a conserved region of 250 amino acids called the cyclin core. It consists of two domains: cyclin N and cyclin C. The cyclin C domain is less conserved and is present in most but not all cyclins , signifying a specific but not a critical function of this domain. The cyclin N domain has the CDK-binding region, which is 100 amino acids long called cyclin box and is the defining domain for cyclins .

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CYCLINS (THREE MAJOR GROUPS) A Type ( cyc A) D Type ( cyc D) B Type ( cyc B) CYC A & CDK CYC D & CDK CYC B & CDK Maintainig S phase & G2/ M transition Controls G2/ S transition by inhoboting retino blastoma related protiens (RBR) resulting in the trannscription of genes involved in DNA replication Controls G2/ M transition

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General mechanism of cyclin -CDK interaction

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CLASSIFICICATION OF MOLECULAR CHAPERONES AND THEIR FUNCTIONS CDK in plants Role CDK A Controls G1/S & G2/M transition CDK B Maintains 2C ratio in the cell CDK C Controls cellular differentiation through RBR inactivation CDK E Cell expansion in leaves and CDK F & CDK D CDK F phosphorylates & activates CDK D, Accelerates S phase & overall growth rate of cell CDK G Helps in cell differentiation CKL (15 types, CKL1-CKL15) A wide range of core cell cycle regulators

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CELL AGING: STRUCTURAL DMAGE THEORIES a) Free radical theory (1957) :- Oxidative damage due to cellular metabolism Aging may be causes by accumulation of some by products of normal cellular metabolism. Reactive oxygen species (ROS) are such substances that are produced by insufficient reduction of substances. These are super-oxide ions, hydroxyl radicals and hydrogen peroxides which are called free radicals. These substances can oxidise the cell membranes, proteins and even nucleic acids.

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b) Mitochondrial theory (1972) Generates ROS through increased electron leakage Sensitive to mutations II. PROGRAMMED THEORIES Genetic theory The rate of DNA damage or mutation enhances aging, because mutation causes synthesis of faulty proteins and enzymes for DNA synthesizing machineries.

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Cellular changes during aging Morphological changes Decline in cell volume decreased weight of organs Accumulation of Exhaustion pigments Cell shape

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Physiological changes Ca ++ accumulate in the cytoplasm. Presence of fewer ribosomes in the cytoplasm Mitochondrial activity is less Chloroplast activity Transport mechanism affected

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Biochemical changes Increase in cholesterol and triglyceride levels. Increase in blood globulin Decrease in alkaline and acid phosphatates Decrease in cellular respiration Increase in concentration of salts, ions, etc in cytoplasm

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CELL DEATH Programmed cell-death (or PCD) is death of a  cell  in any form, mediated by an intracellular program.  PCD serves fundamental functions during both plant and   multicellular animals tissue development.  Apoptosis  and  autophagyare both forms of programmed cell death, however necrosis is a non-physiological process that occurs as a result of infection or injury.

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16 NECROSIS Necrosis, or “accidental” cell death usually caused by extreme trauma or injury to the cell Mechanical damage Exposure to toxic chemicals They (and their organelles like mitochondria ) swell (because the ability of the plasma membrane to control the passage of ions and water is disrupted). The cell contents leak out, leading to inflammation of surrounding tissues.

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17 APOPTOSIS Apoptosis is a form of cellular suicide, since death result from induction of active processes within the cell itself. Shrink Develop bubble-like blebs on their surface DNA and protein in their nucleus degraded Mitochondria break down with the release of cytochrome Break into small, membrane-wrapped, fragments Margination and condensation of nuclear chromatin ( pyknosis ) Cytoplasmic shrinkage Formation of apoptotic bodies.

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Two different reasons for occurring apoptosis 1. Apoptosis is as needed for proper development as mitosis 2 . Apoptosisis needed to destroy cells that represent a threat to the integrity of the organism Extrinsic pathway Intrinsic pathway Pathways of Apoptosis

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FUNCTIONS OF DEVELOPMENTAL CELL DEATH Sculpting/shaping structures/morphogenesis Deletion of unneeded structures Regulation of cell numbers Eliminating abnormal, misplaced or harmful cells Production of structures without organelles

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Characteristics Apoptosis Necrosis Stimuli Physiological or pathological Pathological (injury) Occurrence Single cells Groups of cells Reversibility Limited Limited Cellular level Cell shape Shrinkage and formation of apoptotic bodies Swelling and later disintegration Phagocytosis by other cells Present Absent Exudative inflammation Absent Present Cellular organelles Membranes Blebbing Blebbing proir to lysis Nucleus Convolution of nuclear outline and breakdown (karyorrexis) Disappearance ( karyolysis )

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Thank you It just a beginning….

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