apoptosis popad 2014 v2

7/26/2019 Apoptosis Popad 2014 v2

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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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apoptosis popad 2014 v2

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