chapter 18 apoptosis chapter 18 apoptosis copyright © garland science 2008

Chapter 18Apoptosis

Chapter 18Apoptosis

Copyright © Garland Science 2008

Apoptosis

Two distinct forms of cell death

건강한 성인 : Billions of cells die every hourProgrammed cell death(PCD): idea in 1970s acceptance (20 년 )

:apoptosis (PCD 의 한종류 )

M18.1

apoptosis necrosis

Cell shrinks, Cytoskeletin collapses, 핵막 분해 , DNA 절단Apoptic body-chemically altered:macrophage

SwellBurstSpilling their contentsEliciting inflammatory response

http://18.1-apoptosis.mov/

Programmed cell death morphology in tobacco cells.

Figure 18-2 Molecular Biology of the Cell (© Garland Science 2008)

Sculpting the digits in the developing mouse paw by apotosis

Programmed cell death eliminates unwanted cells

1. 불필요 세포 /조직 /기관제거2. 세포수 조절 ( 간세포 분열 /phenobarbital)3. Quality control: B-/T-lymphocyte cell 제거4. 골수세포 : 백혈구 제거

Figure 18-4a Molecular Biology of the Cell (© Garland Science 2008)

Apoptotic Cells Are Biochemically RecognizableMarkers of apoptosis

TUNEL techniquePhosphatidylserine: 세포막 안쪽 바깥 : Annexin V 로 검출

“eat me” signal“Don’t eat me” signal

Figure 18-4b Molecular Biology of the Cell (© Garland Science 2008)

Apoptotic Cells Are Biochemically RecognizableMarkers of apoptosis

Positively charged 형광색소: 미토콘도리아 inner membrane 의 안쪽

Cytochrome C: released from the intermembrane space of mitochondria


Apoptosis Depends on an Intracellular Proteolytic Cascade That Is Mediated by Caspases

Caspase:Procaspase activation during apoptosis


Apoptosis Depends on an Intracellular Proteolytic Cascade That Is Mediated by Caspases

Procaspase activation during apoptosis

endonuclease

CytoskeletonCell-cell adhesion proteins

Caspase recruitment domain: activation complex


Cell-Surface Death Receptors Activate the Extrinsic Pathway of Apoptosis

The extrinsic pathway of apoptosis activated through Fas death receptors

Tumor necrosis fctor receptor familiy

DISC: Death-inducing signaling complexDecoy receptorFLIP blocking protein


The Intrinsic Pathway of Apoptosis Depends on Mitochondria

Release of cytochrome c from mitochondria during apoptosisbind procaspase-activating adapter protein(Apaf) apoptosome 형성

Recruit initiator procaspase proteins (procaspase-9)


The Intrinsic Pathway of Apoptosis Depends on Mitochondria

The intrinsic pathway of apoptosis

Apoptosis

효소 ?


Bcl2 Proteins Regulate the Intrinsic Pathway of Apoptosis

The three classes of Bcl2



The role of BH123 pro-apoptotic Bcl2 proteins(mainly Bax and Bak) in the release of mitochondrial intermembrane proteins in the intrinsic

pathway of apoptosis

Bax, Bak

• Bax– Bound to mitochondrial outer membrane

• Bak– Located in cytosol, transport into mitochondira

after apoptotic signaling

• Both work on ER and nuclear membrane, activated by ER stress release Ca++ and intrinsic apoptotic pathway



How pro-apoptotic BH3-only and anti-apoptotic Bcl2 proteins regulate the intrinsic pathway of apoptosis

Bid is the link between the two pathways

• Death receptor extrinsic pathway

• The initiator caspase, caspase-8 cleasve Bid producing tBid

• tBid translocates to mitochondria inhibit bcl2

Bid: a proapoptotic BHS-3-only protein


IAPs Inhibit CaspasesA proposed model for the roles of IAPs and anti-IAPs in the control of

apoptosis in mammalian cells

IAP: Inhibitor of apoptosis first identified from vaculovirus.


A proposed model for the roles of IAPs and anti-IAPs in the control of apoptosis in mammalian cells

IAPs Inhibit Caspases


Extracellular Survival Factors Inhibit Apoptosis in Various Ways

The role of survival factors and cell death in adjusting the number of developing nerve cells to the amount of target tissue


Extracellular Survival Factors Inhibit Apoptosis in Various Ways

Three ways that extracellular survival factors can inhibit apoptosis

Bak/bax double mutant in mouse

• Cannot activate intrinsic apoptosis

• But without survival signal, nutrient import is not efficient

• Autophagedie from starvation

UV illumination to human Hela Cells within 24h apoptosis in all cells

from 6 h after illumination to 24 h

Slow apoptosis?or Gradual apoptosis in cell population?

Apoptotic-like regulation of programmed cell death in plants

• Protoplast condensation, nuclear condensation, fragmentation

• A central regulatory role for the mitochondria

• The degradation of the cell and its contents by PCD associated proteases.

• Caspase-like

– Study using caspase inhibitor, substrate

– Lack in caspase ortholog from Arabidopsis genome

• No evidence that cyt c can directly activate AL-PCD proteases.

• No Bcl2 family homologs identified

• Involvement of chloroplast?

Apoptosis (2010) 15:249–256

Schematic representation of AL-PCD

MMP: mitochondrial membrane permeablizationPTP: the perability transition pore

Caspase-independent DNA degradation

• Endo G– No homolog in plant– Mito IMS contain strong Mg2+ dependent nuclease

activity

• AIF/monodehydroascorbate reductase– 5 homologs in Arabidospsis– Antioxidant pathway– DNA-binding defective AIF fails to induce cell

death

Metacaspases

• 9 metacaspases in Arabidopsis• Arginine instead of Aspartic acid• No caspase substrate clevage, no inhibition by

caspase inhibitors• Involvement in PCD of Arabidopsis• Natural substrates?

– TSN(Tudor staphylococcal nuclease) in Norway spruce (유럽가문비 )

– hTSN: caspase substrate, involved in PCD

chapter 18 apoptosis chapter 18 apoptosis copyright © garland science 2008

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