Lecture 18/19: Cell Death/Renewal

apoptosis

programmed cell death w/o cell lysis. the membrane remains intact and there is no leakage of cellular content

apoptotic bodies

smaller fragments cell is separated into during apoptosis

examples of apoptosis

• embryonic morphogenesis

• wiring of developing nervous system (apoptosis when failure to make connections)

• regulation of viability by hormones and growth factors

result of mis-regulation of apoptosis

cancer, alzheimers, AIDs, ischemia (stroke, heart disease)

steps of apoptosis

1. DNA fragmentation

2. chromatin condensation

3. fragmentation of nucleus

4. fragmentation of the cell

necrosis

the process of traumatic cell death that results from acute cellular injury. cells die as the result of cell lysis

result of necrosis

inflammation in the nearby tissue

apoptotic signal

phosphatidylserine on cell surface

phosphatidylserine

on normal cells this is found on the cytosolic face, when found on cell surface this signals apoptosis

Ced-3

caspase involved in apoptosis, activates cell death

Bcl-2 family of proteins

regulates life and death of the cell, can be pro-apoptotic or anti-apoptotic

mitochondria induced apoptosis

• Bcl2 family members Bax and Bak form oligomers in outer membrane of mitochondria

• cytochrome C is released from intermembrane space

• this activates the apoptosome

IAP

apoptosis inhibitors

inhibitors of IAPs function

inhibits inhibitors of apoptosis (IAP) to induce apoptosis

inhibitors of IAPs examples

• Reaper

• Hid

• Grim

2 roles of p53

• cell cycle arrest in G1

• induces cell death after DNA damage

PI-3 kinase pathway

major pathway that signals cell survival and inhibits cell death

G0 cell cycle stage

not dividing, but metabolically active cells. most differentiated cells remain here.

stem cell proliferation

stem cells divide to produce one daughter cell that remains a stem cell and one cell that differentiates to other cell. they exhibit a property of self renewal

totipotent

generate any cell types

pluripotent

generate most cell types

multipotent

generates cell types in specific tissues

platelet derived growth factor (PDGF)

stimulates the proliferation and movement of fibroblasts to exit G0 and proliferate

satellite cells

stem cells of skeletal muscle

LIF (leukemia inhibitor factor) pathway

Jak/STAT pathway

removal of LIF (leukemia inhibitor factor)

leads to differentiation of stem cells

experiments by Takahashi and Yamanaka

showed that only four transcription factors introduced by retroviral expression are capable of transforming somatic cells into induced pluripotent stem cells.

4 transcription factors that can induce pluripotent stem cells

• Oct4

• Sox2

• Klf4

• c-myc

c-myc

acts potentially acts as oncogene

core transcription factors

reprogram adult cells to pluripotent stem cells

the three core transcription factors

• Sox2

• Oct4

• Nanog

transdifferentiation

reprogram somatic cells into other types of differentiated cells