Apoptosis (Kuliah) 2013.ppt

7/24/2019 Apoptosis (Kuliah) 2013.ppt

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APOPTOSIS(CELL DEATH an overview)

Dr Cathy Baker

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HOW DO CELLS DIE?

Kille !y in"#rio#$ a%ent$

In#&e to &o''it $#i&ie

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NECROSIS

APOPTOSIS2


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TA* PE+BELAA,A*

Understand, describe and illustrate

Per!eaan - ne&ro$i$ v$. a/o/to$i$

Per#!ahan 'or0olo%i$ a/o/to$i$1#n%$i a/o/to$i$

+ekani$'e !ioki'ia #ta'aPeran a/o/to$i$ l' /atolo%i

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*e&ro$i$

A/o/to$i$

Patholo%y

+or/holo%i&al&han%e$

1#n&tion

Bio&he'i$try

Le&t#re overview

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*EK,OSIS

L#ka 'ekanik 2 a%ent$ tok$ik

3r#/ $elInte%rita$ 'e'!ran hanr

Sel4$el an or%anel !en%kak5'eleak (/e&ah) an !o&or i$inya

,e$/on In0la'atori$Sel4$el 2 "arin%an lain damaged

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Ke'atian $el oleh nekro$i$

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APOPTOSIS

Pro$e$ !iolo%i$ e$en$ial

Sel4$el 'e'/ /eran l'ke'atiannya 4 told or decide tocommit suicide

Programmed cell death (PCD)

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APOPTOSIS

Bent#k nyata ke'atian $el t#n%%al

Ti%htly re%#late

San%at terlokali$a$iPro$e$ y% 'en%kon$#'$i ener%i

+e'!ran #t#h (tara0 awal)

Pe'!#an%an !an%kai $el y% a'an

*o in0la''ation

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*e&ro$i$

A/o/to$i$

+or/holo%i&al

&han%e$

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PE,BAHA* +O,1OLO3I

SEL

Sel4$el 'eny#$#t an 'en"i terle/a$r $el4$el y% !era'/in%an

Sito$keleton collapses

+itokonria teta/ #t#h

+e'!ran /la$'a 'en%e'!an%kan%ele'!#n% (!le!$) / /er'#kaan

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Membrane blebs during apoptosis

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Nukleus dan kromatin konden

Aggregatespd perifer nukleus

Nuclear envelope disintegrasi

Fragmentasi DNABudding of and breakage into small

membrane wrapped ragments -

apoptotic bodies

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WHAT HAPPENS TO APOPTOTICCELLS AND APOPTOTIC ODIES!

Di"erna # didegradasi ole$ pagosite%akrofag dan sel&sel dendritikSel&sel 'g (erdekatan dlm )aringan*e"ept tinggi dan e+sienTdk dikenali s"r $istologisNo inammation

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*e&ro$i$

A/o/to$i$

+or/holo%i&al

&han%e$

1#n&tion

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F,NCTION OF


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F,NCTION OFAPOPTOSIS?

Pem(ersi$an-peng$ilangan senga)asel&sel spesi+k 'g tak diinginkan

Cara terorganisasi dan terkontrol

Tanpa merusak sel&sel atau )aringanlain

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*eadaan sekitar? 15


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HO+EOSTASIS

*ekonstanan lingkungan internalPergantian )aringan

.uml sel $rs dipeli$ara

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Homeod'nami"s16


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/emo0al of un1anted "ells

Damage

Diferensiasi )aringan dan organVestigial (rudimentary structures

Peru( (entuk )aringan

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Em(r'oni"de0elopment

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6 week$ 7 week$

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Delesi pd neuron immatur 'g(erle(i$an 'g tela$ gagal

mem(tk koneksi sinaptik

T)d pd CNS and PNS

%en"ega$ sel redundant pdsistem s'araf mature

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*e#rolo%i&alevelo/'ent

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!ndometrial breakdown se(elummenstruasi

/egresi 2kemunduran3 )aringanpa'udara laktasi setela$

pen'api$an 2weaning3

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Invol#tion o0 ti$$#e

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*erusakan 2damage3 sel internal

"truktur protein #oyg tdk tepat

Infeksi selViral

Stress"tarvation (kelaparan

DNA damage$oni%ing radiation& '"

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Cell a'a%e

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*e&ro$i$

A/o/to$i$

+or/holo%i&al

&han%e$

1#n&tion

Bio&he'i$try

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BIOCHE+IST,8 O1


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BIOCHE+IST,8 O1

APOPTOSIS

Area intens dlm resear"$

%ekanisme terintegrasi 'g rumit

.au$ le(i$ (an'ak utk diungkap4

Proses inti (ersama

%ensupport peru( morfologis

Proses 5 tingkat

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Sta%e 9 4 The Death Si%nal11

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Sta%e : 4 Inte%ration an Tran$#&tion11

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Sta%e ; 4 E


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Sta%e = 4 Cell ,e'oval11

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A!$en&e or withrawal o0 /o$itive$#rvival 0a&tor$

Pre$en&e o0 ne%ative /ro4a/o/toti&0a&tor$

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Sta%e 94 The Death Si%nal

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S,>I>AL O, POSITI>E

SI3*ALS

Sur0i0al sel mengandalkanpenerimaan stimuli positif

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Withdrawaladl se(ua$sin'al kematian

.alan kegagalan (an'ak sel

Neuronal growt) actor$nterleukin * or lymp)ocytes+ormones

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DEATH O, *E3ATI>E

SI3*ALS

Sin'al utk menginduksi apoptosisDamaged DNA

,V lig)t and rays.)emot)erapeutic drugs

/idants0ree radicals

Stres oksidatifDeat) activators or receptorligands

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WHAT A,E DEATH ACTI>ATO,S?

%olekul 'g (erikatan dg reseptorspesi+k pd permukaan sel

1umour necrosis actor alp)a2ymp)oto/in 1N3 beta3as ligand (.D453

Ikatan deat) activator dgreseptor spesi+kn'a adl sin'alpro&apoptoti"

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STA3E : 4 I*TE3,ATIO* A*D

T,A*SDCTIO*

Sin'al (er$u( dg faseeksekusi melalui tingkatan

integrasi%enggunakan molekulregulatoris positif dan negatif

%eng$am(at6 menstimulasiatau men"ega$ apoptosis

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TO DIE O, *OT TO

DIE?

*eseim(angan 'g terintegrasi antara faktorsur0i0al positif dan sin'al kematian negatif

menentukan takdir sel

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+ESI* I*T,ASELLE, 83 LAI+

TK APOPTOSIS

1iga pemain utama

Famili en7im & Caspases

Famili protein & Bcl-* proteins

8en pengatur - p5# gene

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CASPASES

Famili dr en7im protease

95 isoforms identi+ed

%emp C'steine pd sisi aktif Disintesis s(g prekursor inaktif &

pro"aspase

Tdk semua terli(at dlm apoptosis

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/roo'ain

lar%e $#!#nit$

$'all $#!#nit$

&leava%e

$ite$

Pro"aspase stru"ture

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Procaspase are activated through cleavage

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Re-association of large and small subunits

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Activated caspase has proteolytic activity

Initiatorcaspases

Eectorcaspases

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Eectorcaspases A/o/to$i$e


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CASPASES ARE SPECIALIZED

PROTEASES THAT MEDIATE

APOPTOSIS 11

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BIOL

OGI

MOL

EKU

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APOPTOSISISMEDIATEDBYAN


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APOPTOSIS IS MEDIATED BY AN

INTRACELLULAR PROTEOLYTIC

CASCADE 1

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BIOL

OGI

MOL

EKU

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CELL-SURFACE DEATH RECEPTORS

REGULATETHEEXTRINSIC PATHWAY

OF APOPTOSIS

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BIOL

OGI

MOL

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http://../LECTURE%20IN%20BIOMOL/LECTURE%20MATERIAL%20IN%20MOLECULAR%20BIOLOGY/ANIMATIONS/CELL/APOPTOSIS/Extrinsic%20Pathway%20%202%20ways%20to%20die%20-%20YouTube.flvhttp://../LECTURE%20IN%20BIOMOL/LECTURE%20MATERIAL%20IN%20MOLECULAR%20BIOLOGY/ANIMATIONS/CELL/APOPTOSIS/Extrinsic%20Pathway%20%202%20ways%20to%20die%20-%20YouTube.flvhttp://../LECTURE%20IN%20BIOMOL/LECTURE%20MATERIAL%20IN%20MOLECULAR%20BIOLOGY/ANIMATIONS/CELL/APOPTOSIS/Extrinsic%20Pathway%20%202%20ways%20to%20die%20-%20YouTube.flvhttp://../LECTURE%20IN%20BIOMOL/LECTURE%20MATERIAL%20IN%20MOLECULAR%20BIOLOGY/ANIMATIONS/CELL/APOPTOSIS/Extrinsic%20Pathway%20%202%20ways%20to%20die%20-%20YouTube.flvhttp://../LECTURE%20IN%20BIOMOL/LECTURE%20MATERIAL%20IN%20MOLECULAR%20BIOLOGY/ANIMATIONS/CELL/APOPTOSIS/Extrinsic%20Pathway%20%202%20ways%20to%20die%20-%20YouTube.flvhttp://../LECTURE%20IN%20BIOMOL/LECTURE%20MATERIAL%20IN%20MOLECULAR%20BIOLOGY/ANIMATIONS/CELL/APOPTOSIS/Extrinsic%20Pathway%20%202%20ways%20to%20die%20-%20YouTube.flv


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THE BCL-2 FAMILY OF PROTEINS

REGULATE

THE INTRINSIC PATHWAY OF APOPTOSI

S

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http://../LECTURE%20IN%20BIOMOL/LECTURE%20MATERIAL%20IN%20MOLECULAR%20BIOLOGY/ANIMATIONS/CELL/APOPTOSIS/Apoptosis%20Animation%20%20Intrinsic%20Pathway%20-%20YouTube.flvhttp://../LECTURE%20IN%20BIOMOL/LECTURE%20MATERIAL%20IN%20MOLECULAR%20BIOLOGY/ANIMATIONS/CELL/APOPTOSIS/Apoptosis%20Animation%20%20Intrinsic%20Pathway%20-%20YouTube.flvhttp://../LECTURE%20IN%20BIOMOL/LECTURE%20MATERIAL%20IN%20MOLECULAR%20BIOLOGY/ANIMATIONS/CELL/APOPTOSIS/Apoptosis%20Animation%20%20Intrinsic%20Pathway%20-%20YouTube.flvhttp://../LECTURE%20IN%20BIOMOL/LECTURE%20MATERIAL%20IN%20MOLECULAR%20BIOLOGY/ANIMATIONS/CELL/APOPTOSIS/Apoptosis%20Animation%20%20Intrinsic%20Pathway%20-%20YouTube.flv


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BCL-2 PR!E"#S

Famili (esar dr protein Dinamakan dr "ell

l'mp$oma (rp adl pro&apoptoti"((rp

adl anti&apoptoti"

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BCL4: P,OTEI*S A*D

APOPTOSIS

%ekanisme utama adl regulasipermea(ilitas mitokondria

Stimuli sur0i0al selmenginduksi ekspresi protein"l anti&apoptosis

Deat) signals menginduksiprotein "l pro&apoptoti"

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P$% &E#E A#' P$% PR!E"#

p:; adl tumour suppressor gene

A"ti0e gene produ"t p:; diproduksi dlmrespons t$d DNA and cell damage

%en"ega$ sel men'empurnakan siklus sel

.k damageadl minor < memungkinkanrepair

.k ma)or < menginduksi apoptosis%ekanisme kompleks

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APOPTOTIC T,A*SDCTIO*

PATHWA8S

%ito"$ondrial or intrinsi" pat$1a'

Deat$ a"ti0ator or e=trinsi" pat$1a'

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I*T,I*SIC O, +ITOCHO*D,IAL

PATHWA811

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B&l4:

BaE APOPTOSIS

A$D"

!/cessive apoptosis o 1 )elper cells$sc)aemia

.erebral caused by stroke

.ardiac caused by 9$(myocardialinarction

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8O SHOLD *OW BE ABLE


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TO

,nderstand& describe and illustrate :DiBeren"es ne"rosis 0s apoptosis

%orp$ologi"al "$anges of apoptosisFun"tion of apoptosisPrin"ipal (io"$emi"al me"$anisms

/ole of apoptosis in pat$ologies

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Lau!" et al.#2004$ %&' 6 T(! )("!! *)!+* ,- a+,+),)&. .!// "!,a/


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T(&* */&! a )(! !) T, u*!-u/ )a/!*


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R!'u/a),"* ,- a+,+),*&*


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Apoptosis (Kuliah) 2013.ppt

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