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BIOLOGI - ACHADIAH RACHMAWATI Cell Death Process Programmed Cell Death in Eukaryotes • Cell death can occur by either of two distinct mechanisms – apoptosis or necrosis. • Apoptosis: originally defined according to a set of characteristic ultrastructural features that include nuclear and cytoplasmic condensation, cell fragmentation and phagocytosis. • Necrosis: cell death as the result of injury, disease, or pathological state (usually involves large numbers of cells and is associated with inflammation). Chromatin condenses in multiple small clumps and at later stages, cell membranes and organelles disintegrate. Achadiah Rachmawati 2 Why should a cell commit suicide? Programmed Cell Death in Eukaryotes 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 connections between neurons in the brain Apoptosis is needed to destroy cells – Cells infected with viruses – Cells of the immune system – Cells with DNA damage – Cancer cells 3 CELL DEATH PROCESS 4 1 BIOLOGI - ACHADIAH RACHMAWATI Classical View of Cell Death: Apoptosis vs Necrosis Necrosis vs. Apoptosis Necrosis • • • • Cellular swelling Membranes are broken ATP is depleted Cell lyses, eliciting an inflammatory reaction • DNA fragmentation is random, or smeared • In vivo, whole areas of the tissue are affected Apoptosis • • • • Cellular condensation Membranes remain intact Requires ATP Cell is phagocytosed, no tissue reaction • Ladder-like DNA fragmentation • In vivo, individual cells appear affected Murder? Suicide? 5 6 Stages of Apoptosis NECROSIS vs. APOPTOSIS Induction of apoptosis related genes, signal transduction Wilde, 1999 CELL DEATH PROCESS 7 8 2 BIOLOGI - ACHADIAH RACHMAWATI Biological Roles for Apoptosis Apoptosis in Development • Development • Metamorphosis • Regulation of cell number in tissues (homeostasis and tumorigenesis) • Immune defense (cytotoxic T cell activity) • Develoment of B and T cells via negative selection • Disease: Cancer, autoimmunity, infectious disease etc. 10 Thank You for Your Attention!!!! Definitions • Hyperplasia → Number of cells – Prostate – Endometrium – Breast ducts • Hypertrophy → SIZE of cells – Myocardium – Muscle fibres • Metaplasia → Change of cell TYPE – Cervical where glandular → squamous epithelium – Bronchioles where glandular → squamous epithelium • Dysplasia → Abnormal Development, size, shape, arrangement – Cervical – fibrous Tumour, metastasis, carcinogen 11 CELL DEATH PROCESS 12 3