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Cell Death

Prepared by: NAGA, EILEEN C.


INITIATION OF APOPTOSIS

➢INTRINSIC or MITOCHONDRIAL PATHWAY

➢EXTRINSIC OR DEATH RECEPTOR PATHWAY


➢Inhibits Bcl-2 and Bcl- x
➢Bax and Bak proteins are produced
➢Damaged mitochondrial
membrane
➢Cytochrome c leaks into the
cytoplasm INTRINSIC or
➢Foarmation of Apoptosome
➢Binding of Apoptosome and MITOCHONDRIAL
Apoptosis activating factor or PATHWAY
Apaf-1
➢Caspase cascades.
➢Often involves T lymphocytes
➢Fas Ligand (FasL) on T lymphocyte
binds to Fas receptors on target cell
then binds to Fas Associated Death EXTRINSIC
Domain (FADD)
➢Caspase cascades. PATHWAY
CASPASE FAMILY OF
PROTEASES
➢Caspases are a family of proteases that are
major effectors of apoptotic cell death.
➢Caspase 1 is involved in cytokine
maturation, caspases 4 and 5 are involved
in inflammation, and caspase 14 important
in skin development.
➢Initiator caspases include caspases 2, 8, 9
and 10.
➢Effector caspases include caspases 3, 6,
and 7.
CASPASE FAMILY OF
PROTEASES
➢Caspase cascade
➢The cascade can be activated by various
stimuli: apoptosome and death receptors.
Members of Bcl-2 Family

➢Bcl-2 and Bcl-x


➢Bak and Bax
APOPTOSIS IN DISEASES

➢Cancer
➢Autoimmune conditions:
Rheumatoid arthritis,
systemic lupus, and type
1 diabetes
➢Neurodegenerative
illnesses: Schizophrenia
and Alzheimer’s disease
Laboratory Assessment of Apoptosis

DNA FLOW
LADDERING 01 04 CYTOMETRY
DETECTION
OF
TUNEL APOPTOSIS
METHOD 02 03 ANEXXIN 5
Terminal uridine AFFINITY
deoxynucleotidyl
transferase nick
ASSAY
end labeling
AGING AND
SENESCENCE
Prepared by: NAGA, EILEEN C.
SENESCENCE
Senescence is the
process by which a
mitotic cells SENESCENT
irreversibly stop
dividing and enter a Irreversible cell
Your Text PHENOTYPE
state of permanent cycle arrest
growth arrest
without undergoing
cell death.
Chromatin Modification
modification to Histones
Mechanisms involved in
senescence induction

1 2 3

Mitochondria,
DNA reactive Stem cell
replication oxygen theory of
stress species, and
aging
aging
MOLECULAR MECHANISMS IN SCENESCENCE RESPONSE

The p53 Over expression of p53


gives rise to senescence
Pathway in human cells.
Over expression of p53
The pRb gives rise to senescence
Pathway in human cells.
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