ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the...
-
Upload
lynne-julianna-palmer -
Category
Documents
-
view
226 -
download
4
Transcript of ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the...
![Page 1: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/1.jpg)
Apoptosis Necrosis
Apoptosis is a form of programmed cell death
Apoptosis is responsible for the formation of digits in the developing mouse paw.
Apoptotic cells are biochemically recognizable.Chapter 18
![Page 2: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/2.jpg)
Programmed cell death removes unwanted cells during development.
Apoptotic cells are biochemically recognizable.
In apoptotic cells, phosphatidylserine flips from the inner leaflet to the outer and serves as an “eat me” signal to phagocytic cells.
Apoptosis depends upon an intracellular proteolytic cascade that is mediated by caspases.
The two best understood signaling pathways that can activate a caspase cascade are known as the extrinsic pathway and the intrinsic pathway.
The intrinsic pathway is regulated by a set of pro- and anti-apoptotic proteins that are related to Bcl2.
Either excessive or insufficient apoptosis can contribute to disease.
*
*
*
*
*
*
*
Apoptosis is a form of programmed cell death
![Page 3: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/3.jpg)
Figure 18-5a
Apoptosis depends upon an intracellular proteolytic cascade that is mediated by caspases.
Caspase: They have a cysteine in their active site and cleave substrates at specific aspartic acid residues.
![Page 4: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/4.jpg)
Figure 18-5b
Apoptosis depends upon an intracellular proteolytic cascade that is mediated by caspases.
Initiator
Executioner
Targets
![Page 5: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/5.jpg)
Figure 18-8
The intrinsic pathway of apoptosis
![Page 6: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/6.jpg)
Figure 18-7
Release of cytochrome c from mitochondria during apoptosis
![Page 7: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/7.jpg)
Figure 18-8
The intrinsic pathway of apoptosis
![Page 8: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/8.jpg)
Figure 18-9, 10
Pro-apoptotic Bcl2 proteins stimulate the release of mitochondrial intermembrane proteins
![Page 9: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/9.jpg)
Figure 18-11a Molecular Biology of the Cell (© Garland Science 2008)
The interplay between the pro- and anti-apoptotic Bcl2 proteins determines the activity of the intrinsic pathway
![Page 10: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/10.jpg)
Figure 18-11b Molecular Biology of the Cell (© Garland Science 2008)
The interplay between the pro- and anti-apoptotic Bcl2 proteins determines the activity of the intrinsic pathway
![Page 11: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/11.jpg)
Figure 20-14
Decreased apoptosis can contribute to tumorigenesis
![Page 12: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/12.jpg)
Cancers are monoclonal in origin and multiple mutations are generally required for their progression.
Tumor progression involves successive rounds of random inherited change followed by natural selection.
A small population of cancer stem cells can be responsible for the maintenance of tumors.
Tumor metastasis is a complex, multi-step process.
Cancer-critical genes fall into two major classes: oncogenes and tumor suppressor genes.
Cancer progression typically involves changes in both of these types of genes
The Rb and p53 proteins are two of the most important tumor suppressor gene products for human cancer.
*
*
*
*
*
*
*
CANCER
![Page 13: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/13.jpg)
Figure 20-6 Molecular Biology of the Cell (© Garland Science 2008)
Cancers are generally monoclonal in origin
Evidence from X-inactivation mosaics that demonstrates the monoclonal origin of cancers.
![Page 14: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/14.jpg)
Figure 20-7 Molecular Biology of the Cell (© Garland Science 2008)
Cancer incidence increases with age
![Page 15: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/15.jpg)
Figure 20-11 Molecular Biology of the Cell (© Garland Science 2008)
Tumor progression involves successive rounds of random inherited change followed by
natural selection
![Page 16: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/16.jpg)
Figure 20-36
Oncogene collaboration in mice: Further evidence for the requirement for multiple mutations during tumor formation
![Page 17: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/17.jpg)
Figure 20-16 Molecular Biology of the Cell (© Garland Science 2008)
Cancers may arise
from cancer stem cells
![Page 18: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/18.jpg)
Fig 20-17
Tumor metastasis is a complex multi-step process
![Page 19: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/19.jpg)
Figure 20-29 Molecular Biology of the Cell (© Garland Science 2008)
An assay used to detect the presence of an oncogene:the loss of contact inhibition in culture
![Page 20: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/20.jpg)
Figure 20-37 Molecular Biology of the Cell (© Garland Science 2008)
Some of the major pathway relevant to cancer in human cells
![Page 21: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/21.jpg)
Figure 20-39a Molecular Biology of the Cell (© Garland Science 2008)
Distinct pathways may mediate the disregulation of cell-cycle progression and the disregulation of
cell growth in cancer cells
![Page 22: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/22.jpg)
Figure 20-27
Dominant & recessive mutations that contribute to cancer
![Page 23: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/23.jpg)
Figure 20-33 Molecular Biology of the Cell (© Garland Science 2008)
The types of events that can make a proto-oncogene overactive and convert it into an oncogene.
![Page 24: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/24.jpg)
Figure 20-51
Chronic Myelogenous Leukemia (CML) & the Philadelphia chromosome
Figure 20-5
(Hyperactive Abl)
![Page 25: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/25.jpg)
Figure 20-52 Molecular Biology of the Cell (© Garland Science 2008)
Targeted therapy: the success of GleevecSpecifically targeting the Abl enzyme
Binds to Abl in active site & “locks” the enzyme into an
inactive state
![Page 26: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/26.jpg)
Figure 20-52c Molecular Biology of the Cell (© Garland Science 2008)
Targeted therapy: the success of GleevecSpecifically targeting the Abl enzyme
![Page 27: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/27.jpg)
Figure 20-53 Molecular Biology of the Cell (© Garland Science 2008)
Multidrug Therapy: Combating Resistance
![Page 28: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/28.jpg)
Figure 20-30 Molecular Biology of the Cell (© Garland Science 2008)
The genetic mechanisms that cause retinoblastoma
![Page 29: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/29.jpg)
Figure 20-31
Examples of the ways in which the one good copy of a tumor suppressor locus might be lost through change in DNA sequence,
![Page 30: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/30.jpg)
Figure 20-32
The loss of tumor suppression gene function can involve both
genetic and epigenetic changes
![Page 31: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/31.jpg)
Figure 20-38a
A simplified view of the Rb pathway
![Page 32: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/32.jpg)
Figure 20-38b,c Molecular Biology of the Cell (© Garland Science 2008)
The Rb protein inhibits entry into the cell cycle
![Page 33: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/33.jpg)
Figure 17-62 Molecular Biology of the Cell (© Garland Science 2008)
Mechanisms controllingcell-cycle entry and S-phase
initiation in animal cells
A central role for the Rb protein
![Page 34: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/34.jpg)
Figure 17-62 (part 1 of 3) Molecular Biology of the Cell (© Garland Science 2008)
![Page 35: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/35.jpg)
Figure 17-62 (part 2 of 3) Molecular Biology of the Cell (© Garland Science 2008)
![Page 36: ApoptosisNecrosis Apoptosis is a form of programmed cell death Apoptosis is responsible for the formation of digits in the developing mouse paw. Apoptotic.](https://reader035.fdocuments.net/reader035/viewer/2022062308/56649d145503460f949e92f0/html5/thumbnails/36.jpg)
Figure 17-62 (part 3 of 3) Molecular Biology of the Cell (© Garland Science 2008)
The inactivation of the Rb protein is needed for the entry into S-phase