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Zak, Cells > Lecture 9: Stem Cells & Apoptosis > Flashcards

Lecture 9: Stem Cells & Apoptosis Flashcards

0
Q

Stem Cells

A

Show continuous growth throughout life
Precursors for mature, differentiated cell production
Multipotent and can develop into any number of specialized cells depending on environmental cues
(Basal layer of epidermis, Hematopoietic cells)

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1
Q

Postmitotic Cells

A

Reach highly differentiated state and usually do not divide

Neurons, Skeletal muscle, Cardiac muscle

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2
Q

Quiescent Cells

A

Cells that reach mature differentiated state and do not divide under normal circumstances
Will divide under extraordinary circumstances (Liver cells)

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3
Q

Properties of stem cells

A

Self-renewal
Proliferation
Differentiation
Housed in niches maintained by surrounding stroma cells

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4
Q

What are stroma cells?

A

Connective tissue support in which the parenchyma is located

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5
Q

What is the parenchyma?

A

Masses of tissues similar in type, mostly epithelial derived

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6
Q

Teratoma

A

Neoplasm composed of multiple tissues

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7
Q

Embryonic stem cells

A

Derived from embryonic inner cell mass

Can give rise to all tissue types (except placenta)

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8
Q

Adult stem cells

A

All stem cells other than embryonic

More limited in developmental potential

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9
Q

How is cell growth controlled?

A

By density-dependent inhibition

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10
Q

What is density-dependent inhibition?

A

Cells grow as far as they physically can (in culture dish with edges)
Can be overcome by addition of growth factors or lowering cell density
Lost in neoplastic cells
Cells stop dividing after ~50 mitotic cycles

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11
Q

What does senescent mean?

A

Cell has reached its 50 cell cycles

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12
Q

Telomeres

A

Ends of chromosomes that become shorter with each cell division
Telomerase maintains length of telomeres

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13
Q

T/F: The telomeres on cancer cells get shorter quicker than normal cells.

A

False, the telomeres on cancer calls don’t get shorter allowing them to divide in greater number

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14
Q

Define apoptosis

A

Process of cell death in which cells are genetically programmed and/or signaled to self-destruct in such a way that inflammatory processes are not activated

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15
Q

What is apoptosis used for?

A

Elimination of…
Webbing between digits during development
Unnecessary portion of reproductive system once gender identified
Cells during hormone withdrawal
Cells with damaged DNA due to radiation of chemotherapy
Immature lymphocytes
Infected cells during viral infection

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16
Q

T/F: The cells are degraded from the inside out

A

True

17
Q

What is necrosis?

A

Contents of cell released following breakdown of membranes
Induced by external insults
More likely to activate inflammatory mechanisms

18
Q

What are the 3 phases of apoptosis?

A

Recognition of unbalanced/damaged cell
Execution
Elimination

19
Q

What are the 2 pathways of apoptosis?

A

Extrinsic pathway & Intrinsic pathway

20
Q

How is the extrinsic pathway activated?

A

By external factors binding to “death” receptors

21
Q

How is the intrinsic pathway activated?

A

By leakage of mitochondrial proteins into cytoplasm

22
Q

Describe caspases

A

Exist as inactive “procaspases”

Consist of 4 subunits (2, p10’s & 2, p20’s)

23
Q

Describe procaspases

A

Consist of 2 subunits (p10 & p20)

Bind to receptor via CARD on N-terminal via p20

24
Q

What activates the upstream initiator caspases?

A

Cell-death signal (Fas ligand or tumor necrosis factor-alpha)

25
Q

What do initiator caspases activate?

A

Downstream caspases (executioners)

26
Q

What procaspases do the executioner caspases contain?

A

3, 6, & 7 and have N-terminal called DED (death-effector domain)

27
Q

Explain the first 5 steps of the “Fas Pathway”

A

1) Apoptotic-inducing ligand
2) Paracrine/autocrine mechanism
3) Fas binds to Fas receptor with intracellular domain
4) Fas receptor is trimerized
5) Trimerized Fas recruits FADD (Fas-associated protein with death domain)

28
Q

Explain steps 6-10 of “Fas Pathway”

A

FADD binds to death domain
FADD recruits procaspase 8 via CARD
8) Procaspase 8 is converted to activated caspase 8
9) Caspase 8 = death-inducing cell signaling complex (DISC)
10) Caspase 8 (upstream initiator) activates procaspase 3

29
Q

Explain steps 11-13 of “Fas Pathway”

A

11) Caspase 3 (downstream executioner) cleaves Bid
12) Bid translocates into mitochondria and releases cytochrome c
13) Caspase 3 cleaves ICAD (inhibitor of caspase-activated DNAase)

30
Q

Explain steps 14-17 of “Fas Pathway”

A

14) Cleaved ICAD releases CAD which moves into nucleus to break down DNA
15) Induction of DNA fragmentation/inhibition of repair
16) Release of apoptotic bodies
17) Macrophages phagocytize apoptotic bodies

31
Q

Explain first 4 steps of “Bax Pathway”

A

1) Bax, Bak, Bid, & Bad are proapoptotic proteins
2) Bcl-2 is antiapoptotic protein that prevents Bax from punching holes in mitochondrial membrane
3) Bax/Bcl-2 maintain [equivalent]
4) Bax gets upper hand and punches hole in mitochondrial membrane releasing cytochrome c into cytoplasm

32
Q

Explain steps 5-8 of “Bax Pathway”

A

5) Cytochrome c + Apaf-1 + SIMPS –>apoptosome–>activation of procaspases
6) Induction of DNA fragmentation/inhibition of repair
7) Release of apoptotic bodies
8) Macrophages phagocytize apoptotic bodies

33
Q

What does Apaf-1 stand for?

A

Apoptosis protease activity factor-1

34
Q

What does SIMPS stand for?

A

Soluble intermembrane proteins

35
Q

What is apoptosis-inducing factor (AIF)?

A

Located in intermembrane mitochondrial space
Can leak into cytoplasm
Migrates to nucleus
Binds to DNA and triggers fragmentation

36
Q

T/F: AIF triggers apoptosis in the absence of caspases.

A

True

37
Q

Where does the endosomal-lysosomal pathway occur?

A

In the secondary lysosome

38
Q

Where does the procaspase-caspase pathway occur?

A

In they cytosol

39
Q

What is the Ubiquitin-26S pathway and where does it take place?

A

Takes place in the cytosol
Has 2 steps:
1) Attachment of ubiquitin to protein substrate
2) Degradation of target protein by 26S proteasome

Zak, Cells (17 decks)

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