Apoptosis (Kuliah) 2013.ppt
-
Upload
reivandy-singon -
Category
Documents
-
view
233 -
download
0
Transcript of Apoptosis (Kuliah) 2013.ppt
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
1/90
APOPTOSIS(CELL DEATH an overview)
Dr Cathy Baker
11
/0
4/
15
1
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
2/90
HOW DO CELLS DIE?
Kille !y in"#rio#$ a%ent$
In#&e to &o''it $#i&ie
11
/0
4/
15
NECROSIS
APOPTOSIS2
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
3/90
TA* PE+BELAA,A*
Understand, describe and illustrate
Per!eaan - ne&ro$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
11
/0
4/
15
3
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
4/90
*e&ro$i$
A/o/to$i$
Patholo%y
+or/holo%i&al&han%e$
1#n&tion
Bio&he'i$try
Le&t#re overview
11
/0
4/
15
4
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
5/90
*EK,OSIS
L#ka 'ekanik 2 a%ent$ 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
11
/0
4/
15
5
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
6/90
Ke'atian $el oleh nekro$i$
11
/0
4/
15
6
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
7/90
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)
11
/0
4/
15
7
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
8/90
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 $el y% a'an
*o in0la''ation
11
/0
4/
15
8
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
9/90
*e&ro$i$
A/o/to$i$
+or/holo%i&al
&han%e$
11
/0
4/
15
9
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
10/90
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!$) / /er'#kaan
11
/0
4/
15
10
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
11/90
Membrane blebs during apoptosis
11
/0
4/
15
11
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
12/90
Nukleus dan kromatin konden
Aggregatespd perifer nukleus
Nuclear envelope disintegrasi
Fragmentasi DNABudding of and breakage into small
membrane wrapped ragments -
apoptotic bodies
11
/0
4/
15
12
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
13/90
WHAT HAPPENS TO APOPTOTICCELLS AND APOPTOTIC ODIES!
Di"erna # didegradasi ole$ pagosite%akrofag dan sel&sel dendritikSel&sel 'g (erdekatan dlm )aringan*e"ept tinggi dan e+sienTdk dikenali s"r $istologisNo inammation
11
/0
4/
15
13
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
14/90
*e&ro$i$
A/o/to$i$
+or/holo%i&al
&han%e$
1#n&tion
11
/0
4/
15
14
F,NCTION OF
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
15/90
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
11
/0
4/
15
*eadaan sekitar? 15
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
16/90
HO+EOSTASIS
*ekonstanan lingkungan internalPergantian )aringan
.uml sel $rs dipeli$ara
11
/0
4/
15
Homeod'nami"s16
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
17/90
/emo0al of un1anted "ells
Damage
Diferensiasi )aringan dan organVestigial (rudimentary structures
Peru( (entuk )aringan
11
/0
4/
15
Em(r'oni"de0elopment
17
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
18/90
6 week$ 7 week$
11
/0
4/
15
18
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
19/90
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
11/0
4/
15
*e#rolo%i&alevelo/'ent
19
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
20/90
!ndometrial breakdown se(elummenstruasi
/egresi 2kemunduran3 )aringanpa'udara laktasi setela$
pen'api$an 2weaning3
11/0
4/
15
Invol#tion o0 ti$$#e
20
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
21/90
*erusakan 2damage3 sel internal
"truktur protein #oyg tdk tepat
Infeksi selViral
Stress"tarvation (kelaparan
DNA damage$oni%ing radiation& '"
11/0
4/
15
Cell a'a%e
21
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
22/90
*e&ro$i$
A/o/to$i$
+or/holo%i&al
&han%e$
1#n&tion
Bio&he'i$try
11/0
4/
15
22
BIOCHE+IST,8 O1
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
23/90
BIOCHE+IST,8 O1
APOPTOSIS
Area intens dlm resear"$
%ekanisme terintegrasi 'g rumit
.au$ le(i$ (an'ak utk diungkap4
Proses inti (ersama
%ensupport peru( morfologis
Proses 5 tingkat
11/0
4/
15
23
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
24/90
Sta%e 9 4 The Death Si%nal11
/0
4/
15
24
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
25/90
Sta%e : 4 Inte%ration an Tran$#&tion11
/0
4/
15
25
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
26/90
Sta%e ; 4 E
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
27/90
Sta%e = 4 Cell ,e'oval11
/0
4/
15
27
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
28/90
A!$en&e or withrawal o0 /o$itive$#rvival 0a&tor$
Pre$en&e o0 ne%ative /ro4a/o/toti&0a&tor$
11/0
4/
15
Sta%e 94 The Death Si%nal
28
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
29/90
S,>I>AL O, POSITI>E
SI3*ALS
Sur0i0al sel mengandalkanpenerimaan stimuli positif
11/0
4/
15
Withdrawaladl se(ua$sin'al kematian
.alan kegagalan (an'ak sel
Neuronal growt) actor$nterleukin * or lymp)ocytes+ormones
29
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
30/90
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
11/0
4/
15
30
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
31/90
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"
11/0
4/
15
31
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
32/90
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
11/0
4/
15
32
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
33/90
TO DIE O, *OT TO
DIE?
*eseim(angan 'g terintegrasi antara faktorsur0i0al positif dan sin'al kematian negatif
menentukan takdir sel
11/0
4/
15
33
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
34/90
+ESI* I*T,ASELLE, 83 LAI+
TK APOPTOSIS
1iga pemain utama
Famili en7im & Caspases
Famili protein & Bcl-* proteins
8en pengatur - p5# gene
11/0
4/
15
34
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
35/90
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
11/0
4/
15
35
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
36/90
/roo'ain
lar%e $#!#nit$
$'all $#!#nit$
&leava%e
$ite$
Pro"aspase stru"ture
11/0
4/
15
36
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
37/90
Procaspase are activated through cleavage
11/0
4/
15
37
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
38/90
11/0
4/
15
38
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
39/90
Re-association of large and small subunits
11/0
4/
15
39
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
40/90
Activated caspase has proteolytic activity
Initiatorcaspases
Eectorcaspases
11/0
4/
15
40
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
41/90
Eectorcaspases A/o/to$i$e
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
42/90
CASPASES ARE SPECIALIZED
PROTEASES THAT MEDIATE
APOPTOSIS 11
/0
4/
15
BIOL
OGI
MOL
EKU
LER
42
APOPTOSISISMEDIATEDBYAN
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
43/90
APOPTOSIS IS MEDIATED BY AN
INTRACELLULAR PROTEOLYTIC
CASCADE 1
1/0
4/
15
BIOL
OGI
MOL
EKU
LER
43
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
44/90
CELL-SURFACE DEATH RECEPTORS
REGULATETHEEXTRINSIC PATHWAY
OF APOPTOSIS
11
/0
4/
15
BIOL
OGI
MOL
EKU
LER
44
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 -
7/24/2019 Apoptosis (Kuliah) 2013.ppt
45/90
THE BCL-2 FAMILY OF PROTEINS
REGULATE
THE INTRINSIC PATHWAY OF APOPTOSI
S
11
/0
4/
15
BIOL
OGI
MOL
EKU
LER
45
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 -
7/24/2019 Apoptosis (Kuliah) 2013.ppt
46/90
BCL-2 PR!E"#S
Famili (esar dr protein Dinamakan dr "ell
l'mp$oma (rp adl pro&apoptoti"((rp
adl anti&apoptoti"
11
/0
4/
15
46
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
47/90
11
/0
4/
15
47
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
48/90
BCL4: P,OTEI*S A*D
APOPTOSIS
%ekanisme utama adl regulasipermea(ilitas mitokondria
Stimuli sur0i0al selmenginduksi ekspresi protein"l anti&apoptosis
Deat) signals menginduksiprotein "l pro&apoptoti"
11
/0
4/
15
48
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
49/90
P$% &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
11
/0
4/
15
49
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
50/90
APOPTOTIC T,A*SDCTIO*
PATHWA8S
%ito"$ondrial or intrinsi" pat$1a'
Deat$ a"ti0ator or e=trinsi" pat$1a'
11
/0
4/
15
50
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
51/90
I*T,I*SIC O, +ITOCHO*D,IAL
PATHWA811
/0
4/
15
B&l4:
BaE APOPTOSIS
A$D"
!/cessive apoptosis o 1 )elper cells$sc)aemia
.erebral caused by stroke
.ardiac caused by 9$(myocardialinarction
11
/04
/1
5
84
8O SHOLD *OW BE ABLE
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
85/90
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$ologies
11
/04
/1
5
85
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
86/90
Lau!" et al.#2004$ %&' 6 T(! )("!! *)!+* ,- a+,+),)&. .!// "!,a/
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
87/90
T(&* */&! a )(! !) T, u*!-u/ )a/!*
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
88/90
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
89/90
R!'u/a),"* ,- a+,+),*&*
-
7/24/2019 Apoptosis (Kuliah) 2013.ppt
90/90
11
/04
/1
5
90