Cell Death

Question 0

What are some characteristics of an cell undergoing apoptosis?

Answer 0

1. Loss of surface contact
2. Shrinkage
3. Organelles intact
4. Nuclear changes (chromatin marginalizes on nuclear membrane)

Question 1

T or F. Apoptosis is programmed and inappropriate.

Answer 1

F. Apoptosis is appropriate and programmed. Necrosis is inappropriate and accidental.

Question 2

T or F. Apoptosis is coupled with a heavy inflammatory response.

Answer 2

F. No inflammatory response.

Question 3

During apoptosis, DNA is _________.

Answer 3

cleaved internucleosomally in a very characteristic fashion.

Question 4

What stain stains broken DNA fragments seen during apoptosis?

Answer 4

Tunel stain.

Question 5

Name 5 physiological examples of apoptosis?

Answer 5

1. Embryo development (deletion of interdigital webs)
2. Cell turnover in adult tissues (intestinal crypts)
3. T-cell clonal deletion
4. Normal involutional processes (ovary, breast,
   endometrium)
5. Atrophic processes (prostate)

Question 6

What 4 pathological conditions that involve apoptosis? (not specific diseases)

Answer 6

1 Atrophic processes (renal, hepatic)
2 Viral infections (HIV)
3 Immune-mediated cell killing (rejection, graft vs host)
4 Cellular injury (radiation, chemotherapy, toxins)

Question 7

Name 5 diseases associated with increased apoptosis.

Answer 7

1. AIDS
2. Neurodegenerative disorders(Alzheimer’s, Parkinson’s, Amyotrophic lateral sclerosis, Retinitis pigmentosa, Cerebellar degeneration
3. Myelodysplastic syndromes (Aplastic anemia)
4. Ischemic injury (MI, Stroke, Reperfusion injury)
5. Toxin induced liver disease– Alcohol

Question 8

What diseases are associated with inhibition of apoptotic activity?

Answer 8

1. Cancer
2. Autoimmune disorders
3. Viral infections

Question 9

Name 4 mechanisms of apoptosis stimulation.

Answer 9

• Organelle dysfunction (intrinsic)
• Death receptor activation (extrinsic)
• DNA damage
• Abnormal protein folding/accumulation

Question 10

Name an example of organelle dysfunction causing apoptosis.

Answer 10

Mitochondrial dysfunction, major regulator of apoptosis. Cellular stress causes Bax pokes holes in mito, mito release cyt c (for apoptosome) and AIF (nuclear fragmentation).

Question 11

Name 2 examples of cell death receptors (extrinsic).

Answer 11

Activation of death receptor (FAS, TNF) on extracellular membrane.

Question 12

Both mitochondrial driven (intrinsic) and death receptor (TNF, FAS) mediated apoptosis involves what type of enzymes?

Answer 12

Caspases, causes morphological changes in cell, major effector of apoptotic cell death

Question 13

T or F. Caspases are synthesized as proenzyme and activated by cleavage

Answer 13

True.

Question 14

What happens to cells during necrosis

Answer 14

dilatation of organelles, ribosome disaggregation, mito swelling, blebbing, inflammatory response

Question 15

T or F. Like apoptosis, DNA is fragmented into characteristic bands during necrosis.

Answer 15

F. Smear.

Question 16

What are differences between apoptosis and necrosis?

Answer 16

DNA: internucleosomal ladder cleavage vs random fragments
Nucleus: Chromatin margination vs Pyknosis (shrinkage)
Membrane: Persists late vs. compromised early
Mito: appears normal vs. swollen (ca2+)
Inflam: no vs. yes
Pattern: single cell vs. multiple cells affected
Cell volume: decreases vs. increases
Cell fragmentation: Yes (apoptotic bodies) vs No (cell lysis)

Question 17

What can trigger necrosis?

Answer 17

• Acute energy depletion
– ischemia, glutamate receptor overactivation, hypoglycemia
• Trauma
• Harsh environments
–– strong detergents, acids, oxidants, heat, cold, excessive strong detergents acids oxidants heat cold excessivemechanical strain)
• Excessive accumulation of ROS
• Extensive DNA damage

Question 18

What are some mechanisms of necrosis?

Answer 18

• Perturbation of ion homeostasis
– Ca++, Na+, Mg++, Zn++
– Acidosis
– Animal models- “degenerins” (ion channels)
• Protein degradation
– Lysosomes
– Calpains
– Caspases

Question 19

What is cell death with mixed features (apoptotic, necrotic)?

Answer 19

Paraptosis

Question 20

Can necrosis be programmed?

Answer 20

Yes.

Question 21

What are some pharmacological approaches to block cell death?

Answer 21

• Ca chelators, Ca channel blockers, Ca binding proteins,
• Caspase inhibitors
• Protease inhibitors
• Glutamate receptor antagonists (Memantine)
• Growth factors (BDNF)
• Cytokines
• Antioxidants

Question 22

What preventative measures are taken against cell death during hibernation?

Answer 22

– Decr expression of apoptotic proteins
– Incr expression of anti-apoptotic proteinsp pp p
– Decr caspase activation

Question 23

What are some characteristics of autophagy?

Answer 23

Role in degradation/recycling of cellular components. Autophagic vacuoles accumulate in cells, survival during starvation, type 2 cell death (lysosomal)