Programmed Cell Death

Size: px

Start display at page:

Download "Programmed Cell Death"

Holly Payne
6 years ago
Views:

1 Programmed Cell Death Dewajani Purnomosari Department of Histology and Cell Biology Faculty of Medicine Universitas Gadjah Mada

2 What is apoptosis? a normal component of the development and health of mul6cellular organisms. response to a variety of s6muli and during apoptosis they do so in a controlled, regulated fashion. Apoptosis, or programmed cell death, 2

3 distinct from necrosis in which uncontrolled cell death leads to lysis of cells, in;lammatory responses and, potentially, to serious health problems. a process in which cells play an active role in their own death (which is why apoptosis is often referred to as cell suicide) What is apoptosis? 3

4 Apoptosis is a normal self- destruc3on mechanism 4

5 Stages of apoptosis (A). The breakdown of chroma6n in the nucleus (B). Cells con6nue to shrink (C), packaging themselves into a form that allows for their removal by macrophages (D) Small vesicles called apopto6c bodies are also some6mes observed

6 Apoptosis is a normal self- destruc3on mechanism Caspases are central executioner of apoptosis Caspase: Cysteine Aspartate Speciﬁc ProteASEs 09/12/14 d.purnomosari@ugm.ac.id 6

7 7 Figure 18-5a Molecular Biology of the Cell ( Garland Science 2008)

8 Apoptosis is mediated by intracellular proteolytic cascade 8 Figure 18-39b Essential Cell Biology ( Garland Science 2010)

9 9 Mechanisms that induce apoptosis

10 intrinsic signals à cellular stress. Cellular stress exposure to radia6on or chemicals or viral infec6on growth factor depriva6on or oxida6ve stress caused by free radicals. In general intrinsic signals ini6ate apoptosis via the involvement of the mitochondria à the rela6ve ra6os of the various bcl- 2 proteins Apoptosis induction 10

11 Pro-survival and pro-apoptotic proteins 11 Figure 9.25a The Biology of Cancer ( Garland Science 2007)

12 Intrinsic apoptosis pathway starts in mitochondria Figure Essential Cell Biology ( Garland Science 2010) 12

13 Apoptosis is a normal self- destruc3on mechanism 13 Puma: p53 upregulated modulators of apoptosis

14 14

15 The role of BH123 in intrinsic pathway 15 Figure Molecular Biology of the Cell ( Garland Science 2008)

16 An6 apopto6c Bcl- 2 regulate the intrinsic pathway 16 Figure 18-11a Molecular Biology of the Cell ( Garland Science 2008)

17 Extrinsic signals the binding of death inducing ligands to cell surface receptors called death receptors cytotoxic T-lymphocytes using the enzyme granzyme. Apoptosis induction 17

18 Extrinsic apoptosis pathway starts when death receptor is activated 18 Figure 18-6 Molecular Biology of the Cell ( Garland Science 2008)

19 Death receptor 19 Figure 9.31a The Biology of Cancer ( Garland Science 2007)

20 Apoptosis is a normal self- destruc3on mechanism Granzyme pathway 20

22 Apoptosis in health and disease responsible for shaping tissues and organs in developing embryos. (the apoptosis of cells located in- between the toes allows for their separation) during the normal development of multicellular organisms and continues throughout adult life. important part of the regulation of the immune system (Thymus maturation) 22

23 23

24 24 Figure Q18-1 Molecular Biology of the Cell ( Garland Science 2008)

25 too little apoptosis à cancer mutations may prevent cells from undergoing apoptosis. tumors can be difficult to kill à resistant to chemical or damaging agents Understanding how apoptosis is regulated in cancer is therefore of major interest in the development of treatments for this disease. Apoptosis in health and disease 25

26 too much apoptosis For example in neurodegenerative diseases such as Parkinson's or Alzheimer's Diseases apoptosis is thought to account for much of the cell death and the progressive loss of neurons. Apoptosis in health and disease 26

27 trophoblast cells to remodel the maternal blood vessels and help establish and maintain a successful pregnancy. excessive apoptosis of the trophoblast cells is thought to be implicated in the failure to fully remodel the maternal environment that is observed in complications of pregnancy such as preeclampsia. Apoptosis in health and disease 27

28 progression of many auto-immune diseases. rheumatoid arthritis excessive proliferation of synovial cells is thought to be due in part to the resistance of these cells to apoptotic stimuli. Apoptosis in health and disease 28

29 Apoptosis 29

30 30

Cell Death & Trophic Factors II. Steven McLoon Department of Neuroscience University of Minnesota

Cell Death & Trophic Factors II Steven McLoon Department of Neuroscience University of Minnesota 1 Remember? Neurotrophins are cell survival factors that neurons get from their target cells! There is a