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APOPTOSIS
By
Dr.M.Anthony David
Professor of Physiology
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Apoptosis is
Programmed cell death
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Greek Apo meaning awayfrom Ptosismeaning todroop or to fall.
Apoptosis :Physiological: To fallaway : ell s!icide
"ecrosis: a pathologicaldestr!ction of cells : ell m!rder
ETYMOLOGY
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Necrosis or Apoptosis
NE!O"#" APOPTO"#"
ell #!rder ell S!icide
Passi$e Acti$e
Pathological PhysiologicalSwelling % &ysis
seenondensation % ross'
linking seen
(issipated PhagocytosedIn)ammation seen "o in)ammation
*+ternally ind!ced Internally or e+ternallyind!ced
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ommon in ,etal de$elopment as wellas in ad!lthood.
ommon e+amples:#any ne!rons !ndergo apoptosisd!ring remodelling of the "S
Inappropriate clones in the imm!nesystem.-emo$ing the wes etween /ngers
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P$Y"#OLOG#AL %APOPTO"#"
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(isappearance of the #!llerian System inthe males
-emo$al of the *ndometri!m d!ring
menstr!ationThe epidermal layers of o!r skin arecontin!ally replaced y germinal
epitheli!m.0orn o!t cells remo$ed y apoptosisSame with the enterocytes on theIntestinal $illi and micro$illi
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P$Y"#OLOG#AL %APOPTO"#"
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A!toimm!ne diseases*+ample : Systemic &!p!s
*rythematos!s"e!rodegenerati$ediseasess :*g : Parkinson1s disease
arcinomas: ancers*g : O$arian ancer2 Testic!larcancer 7
APOPTO"#" % Pathological
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3. (eath signal : Initiators of cell death:i. *+ternal
ii. Internal
4. ommitment to die : -eg!lators of
Apoptosisi. 5&'42 5A(2 5A62 p78etc
8. *+ec!tion of death : aspase Pathwaysi. ,as receptor acti$ation
ii. eramide generationiii. ("A damage
9. *ng!lfment : Phagocytosis
Mechanis& of Apoptosis
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STAG*S O, APOPTOSISHealthy cell
DEATH SIGNAL
Commitment to die (reversible)
EXECTI!N (irreversible)
(ead cell condensed2 crosslinked;
ENGL"#ENT $ %HAG!C&T!SIS
DEG'ADATI!N
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ells are alanced etween life and deat
DAMAGE %hysioloical death sinals
DEATH SIGNAL
P!O'
APOPTOT#P!OTE#N"
ANTIA%!%T!TIC
%'!TEINS
BAX
BAD
BCL-2
BCL-XL
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A%!%T!SIS* Controlled %rocess
Physiological Intrinsic
receptor pathway damage pathway
MITOCHONDRIAL SINALS
Cas+ase cleavae cascade
!rderly cleavae o, +roteins and DNA
Crosslin-in o, +roteinsA+o+totic bodies
%HAG!C&T!SIS11
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A%!%T!SIS* control
'ece+tor +ath.ay*
Death rece+tors*("AS/ TN"'/ etc)
"AS liand TN"
Death
domains
Adaptor proteins
%rocas+ase 0 (inactive) Cas+ase 0 (active)
%roe1ec2tion cas+ase (inactive)E1ec2tion cas+ase (active)
Death#IT!CH!ND'IA
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APOPTOSIS: control
Intrinsic pathway !damage"#
Mitochondria
Cytochrome c release
Pro-caspase clea!a"e
Pro-e#ec$tion caspase %&' clea!a"e
Caspase %&' clea!a"e o( cell$lar proteins)
*$clease acti!ation)
+tc,
Death
BAX
BAD
BCL-XL
BCL-2+
-
Sma!D"A#$%
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A%!%T!SIS* in embryoenesis
#or+hoenesis (eliminates e1cess cells)*
e33 .eb s+aces bet.een diits
Selection (eliminates non,2nctional cells)*
e33ne2rons
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A&%&'%S"S( in em)r*oenesis
Or"an sie %eliminates e#cess cells':
,eression o d.t s*stem d.rin se/ dierentiation
e M.erian d.ts
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A%!%T!SIS* im+ortant in imm2nity
Imm2nity (eliminates danero2s cells)*
Sel, antienreconi4in cell
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A%!%T!SIS* in ad2ltsTiss2e remodelin (eliminates cells no loner needed)*
5irin mammary land Late +renancy/ lactation Invol2tion
(non+renant/ nonlactatin
A+o+tosis
A+o+tosis- Testosterone
%rostate land
%renant 2ter2s Invol2tion a,ter deliveryA+o+tosis
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A%!%T!SIS* in ad2ltsTiss2e remodelin (eliminates 2nnecessarycells)*
'estin lym+hocytes 6 antien (e33 in,ection) antien (e33 recovery)
A+o+tosis
Steroid imm2nos2++ressants* -ill
Lym+hocytes by a+o+tosisLym+hocytes +oised to die by a+o+tosis
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APOPTOSIS : in ad!ltsMaintains oran sie and .ntion
A+o+tosis6 cell division
Cells lost by a+o+tosis are re+laced by cell division
E33 Cyclical sheddin o, endometri2m
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Aging : *+cessi$e % &ess of apoptosis*+cessi$e Apoptosis d!e to acc!m!latedo+idati$e damage a!ses tiss!e degeneration
&ess Apoptosis d!e to defecti$esensors
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A%!%T!SIS* %atholoical (in Disease)
T!! #CH* Tiss2e atro+hy
T!! LITTLE* Hy+er+lasia
Ne2rodeeneration
Thin s-in
etc
CancerAtherosclerosis
etc
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Ne(rons cannot replace the&selvesnor&ally
Die d(e to loss of proper connections) lossof proper gro*th factors +e.g. NG,-) or
da&age +especially oidative da&age-Ne(ronal dysf(nction or da&age res(lts in
loss of synapses"ynaptosis +reversi/le-
Apoptosis +irreversi/le-Ne(rodegenerative diseases incl(de%PA!0#N"ON1" D#"EA"E
AL2$E#ME!1" D#"EA"E
$3NT#NGTON1" D#"EA"E 22
APOPTO"#"% !ole in DiseaseNe(rodegeneration
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Apoptosis eliminates damaged cellsdamage >? m!tations >? cancerT!mor s!ppressor p78 controls senescence
and apoptotic responses to damage#ost cancer cells defecti$e in apoptoticresponse
=igh le$els of anti'apoptotic proteins Or&ow le$els of pro'apoptotic proteinsa!ses A"*-
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APOPTO"#"% !ole in Diseaseancer
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Programmed cell death is physiological It has a role to play in the fetalde$elopment.
It also helps !s in ad!lt li$es in therecycling of certain tiss!es
It helps in the #enstr!al cycle in women
In disease it is seen in cancers and inne!rodegenerati$e diseases
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Apoptosis % A !evie*
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