Cell renewal, cell death and apoptosis

Question 1

the balance between the production of new cells and cell death that maintains the appropriate number of cells in a tissue.

Answer 1

homeostasis

Question 2

What are reversible functional and structural responses to physiologic stresses; hypertrophy, hyperplasia, atrophy, metaplasia

Answer 2

adaptation

Question 3

What is the state where cells are no longer able to adapt; ATP depletion, cell swelling, alterations in intracellular organelles, such as mitochondria and the cytoskeleton

Answer 3

cell injury

Question 4

the end result of progressive and irreversible cell injury. Cells die by one of two mechanisms; necrosis or apoptosis

Answer 4

cell death

Question 5

Apoptosis and necrosis have different characteristics; What are the differences

Answer 5

differ in their morphology, mechanisms, and roles in physiology and diseases.

Question 6

What is an
Accidental cell death from acute injury by external factors. It is the ungoverned, irreversible, and premature death of cells and living tissues.

Answer 6

Necrosis (detrimental, not natural)

Question 7

What is a
Programmed cell death (cell-suicide program).
It is carefully regulated.
It balances cell proliferation and maintains constant cell numbers.
It eliminates “non-functioning, unwanted, damaged, or potentially dangerous” cells.

Answer 7

apoptosis (beneficial, natural)

Question 8

These are causes of:
Pathological conditions
 Trauma; injury, burns, shock
 Lack of blood flow; hernia,
cancer, hypoxia, stroke, 
 myocardial infarction
 Infection; viruses to tapeworms 
 Chemicals; poisons 
 Inflammation;
 Nutritional imbalances;

Answer 8

necrosis

Question 9

o
Physiological conditions to cause (blank):
 The programmed destruction of cells during embryogenesis. For example, during development of a limb, tissue present between the digits must be removed. This occurs through localized apoptosis.
 Normal cell loss in proliferating cell populations.
 Involution of hormone-dependent tissues upon hormone withdrawal.

Answer 9

apoptosis

Question 10

What condition can undergo apoptosis or necrosis?

Answer 10

myocardial infarction

Question 11

o Pathophysiological conditions to cause (blank):
 DNA damage; anticancer drugs, radiation, and hypoxia.
 Accumulation of misfolded proteins leading to endoplasmic reticulum (ER) stress.
 Cell death in certain infections, particularly viral infections.
 Pathologic atrophy of organs and tissues as a result of stimuli removal.
 Cytotoxic T cell-induced cell death.
 Cell death that occurs in heart diseases.

Answer 11

apoptosis

Question 12

When cells are stressed it causes (blank)
If cell injury is irreversible what happens to the cell?
This happens in what type of cell death?

Answer 12

reversible or irreversible injury
Swelling, complete dissolution of nucleus, plasma membrane disrupted, enzymatic digestion of cell contents
Necrosis

Question 13

Apoptosis results in what happening to the cell?

Answer 13

shrinkage, chromatin condensation + fragmentation + become apoptopic bodies, PM remains intact, cellular contents may be released in apoptopic bodies.

Question 14

apoptotic bodies contain what?

Answer 14

fragmented nucleus

Question 15

apoptotic cells express (blank) signals which recruit and are recognized by (blank).

Answer 15

eat me.

Phagocytes

Question 16

What are some notable eat me signals of apoptotic cells?

Answer 16

• “Flipped-out” phosphatidylserine which is restricted to the inner leaflet of the plasma membrane.
• Thrombospondin
• An adhesive glycoprotein
• Natural antibodies and proteins of the complement system, notably C1q
• Soluble factors

Question 17

This process of phagocytosis of apoptotic cells is (blank) , often within minutes, and inflammation is (blank).

Answer 17

efficient

absent.

Question 18

(blank) cells swell and lyse; the contents are released into the extracellular space and cause inflammation.

Answer 18

Necrotic

Question 19

Apoptotic signaling pathways:

(blank) are the effectors of apoptosis

Answer 19

Caspases

Question 20

Activation of what molecular will lead to a cascade and eventual apoptosis? i.e the ultimate executioner of apoptosis

Answer 20

caspase

Question 21

Initiation of apoptosis occurs principally by signals from two distinct pathways

Answer 21

Intrinsic or mitochondrial pathway

Extrinsic or death receptor–initiated pathway

Question 22

(blank) have cysteine (C) residues at their active sites and cleave after aspartic acid (Asp) residues in their substrate proteins.
Cleave nearly 100 different cell target proteins.

Answer 22

Caspases

Question 23

What are four different targets of caspases?

Answer 23

• ICAD inhibitor of DNAse, (frag of DNA)
• Nuclear lamins (frag of nucleus)
• Cytoskeletal proteins actin, myosin, alph-actinin, tubulin, vimentin (frag of membrane)
• Golgi matrix proteins (frag of golig)

Question 24

(blank) act as either initiators or effectors of apoptosis

Answer 24

caspases

Question 25

In normal cells, caspase is typically (blank)

Answer 25

inactive

Question 26

What is the caspase pathway?

Answer 26

* Each caspase is initially made as an inactive proenzyme (procaspase). Some procaspases are activated by proteolytic cleavage by an activated caspase: two cleaved fragments from each of two procaspase molecules associate to form an active caspase, which is a tetramer of two small and two large subunits; the prodomains are usually discarded, as indicated. * The first procaspases activated are called initiator procaspases, which then cleave and activate many executioner procaspase molecules, producing an amplifying chain reaction (a proteolytic caspase cascade). The executioner caspases then cleave a variety of key proteins in the cell.

Question 27

What are the initiator caspases?

Answer 27

2,8,9,10

Question 28

What are the executioner caspases?

Answer 28

3,6,7

Question 29

What does the intrinsic or mitochondrial pathway of initation of aptosis consist of?

Answer 29

Members of the Bcl-2 family act at the mitochondria. | Cytochrome c released from mitochondria triggers caspase activation.

Question 30

Bcl-2 family members regulate the intrinsic pathway | by controlling mitochondrial release of (blank)

Answer 30

cytochrome c

Question 31

(blank) domain mediates a direct binding interaction between one pro-apoptotic protein and one anti-apoptotic protein to form heterodimers.

Answer 31

The BH3

Question 32

(blank) often acquire mutations that allow them to alter the balance between pro- and anti-apoptotic proteins, making it less likely for them to commit suicide even under conditions when normal cells would

Answer 32

Cancer cells

Question 33

(blank) is the only domain shared by all BCL-2 families.

Answer 33

BH3

Question 34

Bcl-2 family proteins regulate the intrinsic pathway | by controlling mitochondrial release of (blank)

Answer 34

anti-IAP proteins

Question 35

Caspases are also regulated by a family of proteins called the (blank)

Answer 35

IAP (inhibitors of apoptosis) anti-IAP proteins.

Question 36

In the absence of an apoptotic stimulus, the IAP proteins are located in the cytosol and bind to and inhibit any spontaneously activated (blank) .

Answer 36

caspases

Question 37

When an apoptotic stimulus activates the intrinsic pathway, anti-IAP proteins are released from mitochondria through activated (blank) proteins, and bind to and block the inhibitory activity of the IAPs. At the same time, the released cytochrome c triggers the assembly of apoptosomes, which can now activate a caspase cascade, leading to apoptosis.

Answer 37

BH123

Question 38

Describe the cytochrom c activated caspase cascade:

Answer 38

release of cyt c->activationf of ApafI->gain dATP-> forms apoptosome-> recruits procaspase 9-> activates executioner procaspases->capase cascade leads to apoptosis

Question 39

(blank) is a particularly dangerous form of cell stress, because mutations can lead to the development of cancer.

Answer 39

DNA damage

Question 40

If the DNA damage is too great to be repaired successfully,(blank) are activated, and they then phosphorylate (activates) and stabilize p53 tumor suppressor protein.

Answer 40

ataxia telangiectasia mutated (ATM) and Chk2 protein kinases

Question 41

When you have a large increase in p53, what will p53 target?

Answer 41

Cdk inhibitor p21, which inhibits Cdk2/cyclin E complexes, halting cell cycle progression in G1 (cell cycle arrest). BH3-only proteins PUMA and Noxa, which activate BH123 proteins Bax and Bak, leading to mitochondrial release of cytochrome c and activation of caspase-9 (apoptosis).

Question 42

What does p53 mediate?

Answer 42

cell cycle arrest and apoptosis in response to DNA damage.

Question 43

Summarize the extrinisc or death receptor-intiated pathway?

Answer 43

Fas ligand (polypeptides in Tumor necrosis family (TNF)) signal cell death by activating cell surface death receptors, as happens in the immune system when T cells kill their target cells by producing Fas ligand.

Question 44

Cell surface death receptors directly activate a distinct initiator caspases, caspase (blank or blank)

Answer 44

caspase-8 or 10.

Question 45

Killer T cell-induced apoptosis via (blank)

Answer 45

Fas death receptor

Question 46

describe the killer T cell-induced apoptosis via Fas death recepter pathways

Answer 46

Fas ligand, binds to Fas death receptor Fas recruits adaptor protein FADD (fas -associated Death domain) FADD recruits initiator procaspase forming death-inducing signaling complex (DISC) Procaspase molecules on DISC get close which activates their cleavage and stabilizes the activated protease which is now a caspase. Activated caspase cleaves and activates executioner procaspaes which creates caspase cascade->apoptosis

Question 47

TNF and other cell death receptor ligands consists of three polypeptide chains, so their binding to cell death receptors induces receptor (blank)

Answer 47

trimerization.

Question 48

are their interconnections between intrinisc and extrinsic pathway?

Answer 48

Yes via TNF and Capase 8

Question 49

How does capase-8 participate in the extrinsic pathway of apoptosis?

Answer 49

Capase-8 is recruited to the receptor and activated via interaction with adaptor molecules. Once activated, caspase-8 can directly cleave and activate effector caspases

Question 50

How does capase-8 participate in the intrinsic pathway of apoptosis?

Answer 50

caspase-8 cleaves the BH3-only protein Bid, which activates the intrinsic pathway of apoptosis, leading to caspase-9 activation

Question 51

Early development is characterized by the rapid proliferation of (blank) , which then differentiate to form the specialized cells of adult tissues and organs.

Answer 51

embryonic cells

Question 52

As cells differentiate, their rate of proliferation usually (blank), and most cells in adult animals are arrested in the (blank) stage of the cell cycle.

Answer 52

decreases | G0

Question 53

In order to maintain a constant number of cells in adult tissues and organs, cell death must be balanced by cell (blank) .

Answer 53

proliferation

Question 54

Most differentiated cells in adult animals are no longer capable of (blank). If these cells are lost they are replaced by proliferation of cells derived from .

Answer 54

proliferation | self-renewing stem cells

Question 55

Some types of differentiated cells that are normally arrested in G0 stage of the cell cycle can....?

Answer 55

retain the ability to resume proliferation as needed, to repair damaged tissue.

Question 56

What are some differentiated cells that are normally arrested in G0 phase of cell cycle and are able to regenerate?

Answer 56

endothelial cells (VEGF angiogenesis in ischemic myocardium), epothelial cells (liver), fibroblastes (PDGF i.e. cut or wound)

Question 57

What does this describe: a subpopulation of less differentiated self-renewing cells present in most adult tissues. retain the capacity to proliferate and replace differentiated cells throughout the lifetime of an animal. divide asymmetrically to produce one daughter cell that remains a stem cell and one progenitor cell that further divides and terminally differentiates

Answer 57

stem cells

Question 58

Many types of cells that have short life spans and must be continually replaced by proliferation of stem cells include:

Answer 58

blood cells, sperm, epithelial cells of the skin and lining the digestive tract, skeletal muscle, nervous system, and heart.

Question 59

(blank) that line the intestines are exposed to harsh environment and live only a few days before they die by apoptosis. These cells have new cells that are derived from the continuous but slow division of stem cells at the (blank) of intestinal crypts, which were identified in 2007. Stem cells give rise to a population of (blank), which proliferate for 3-4 divisions and then differentiate into the three types of the colon surface epithelium (an absorptive epithelial cells and two secretory cells, called goblet cells and enteroendocrine cells).

Answer 59

Epithelial cells bottom transit-amplifying cells

Question 60

(blank) is a clinical procedure in which transplantation of bone marrow stem cells is used in the treatment of cancer and diseases of the hematopoietic system.

Answer 60

Hematopoietic stem cell transplantation (or bone marrow transplantation

Question 61

What type of cells are used for skin grafts to treat patients with burns, wounds, and ulcers.

Answer 61

Skin epithelial stem cells

Question 62

Skin epithelial stem cells and hematopoietic stem cell transplants are what?

Answer 62

applications of adult stem cells

Question 63

What is an advantage of the use of adult stem cells in clinics:

Answer 63

Transplantation from the patient himself eliminates the potential complication of graft rejection by the immune system.

Question 64

What are some disadvantages of adult stem cell therapy?

Answer 64

Isolation and culturing pure stem cell populations are difficult. Stem cells have not yet been identified in many adult tissues. Adult stem cells do not have pluripotency - the capacity to develop into all of the different types of cells in adult tissues.

Question 65

(blank) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage embryo, first cultured from mouse embryos in 1981.

Answer 65

embryonic stem cells

Question 66

What are advantages to clinical applications of ES:

Answer 66

ES cells can be grown indefinitely as pure stem cell populations. They can be directed to differentiate to a variety of cell types (pluripotency). Clinical transplantation therapies based on ES cells may provide the best hope for treatment of diseases such as Parkinson’s and Alzheimer’s disease, diabetes, and spinal cord injuries.

Question 67

What are some disadvantages to ES?

Answer 67

Cell culture conditions to obtain specific differentiated cell types are not yet fully characterized. Ethical concerns with respect to the destruction of embryos.

Question 68

What are the basic science applications of placing ES into mice?

Answer 68

They can be used to introduce altered genes into mice. They provide an outstanding model system for studying the molecular and cellular events associated with cell differentiation.

Question 69

What does this describe: the basic procedure of animal cloning in which the nucleus of an adult somatic cell is transferred to an enucleated egg. In 1997, Dolly arose from the nucleus of a mammary epithelial cell that was transplanted into an unfertilized egg in place of the normal egg nucleus. This type of cloning in mammals is a difficult and inefficient process.- only 1-2% of embryos generally give rise to live offspring.

Answer 69

Somatic cell nuclear transfer

Question 70

What does this describe: , a nucleus from an adult human cell would be transferred to an enucleated egg, which is then used to produce an early embryo in culture. ES cells are then cultured form the cloned embryo and used to generate appropriate types of differentiated cells for transplantation therapy.

Answer 70

therapeutic cloning

Question 71

What are the advantages and disadvantages of therapeutic cloning?

Answer 71

advantages= pluripotency, no immune rejection, could correct inherited disease Disadvantages: low efficiency, culture conditions aren't understood, ethical concern w/ cloning and destruction of embryo

Question 72

What are pluripotent stem cells artificially derived from a non-pluripotent cell - typically an adult somatic cell - by inducing a "forced" expression of specific genes.

Answer 72

iPS stem cell

Question 73

What a big disadvantage of iPS?

Answer 73

risks to cause cancer

Question 74

What can lead to disease caused by apoptosis?

Answer 74

either excessive or insufficient apoptosis

Question 75

Is this from excessive or insufficient apoptosis: Cancers Autoimmune diseases Hematological diseases

Answer 75

insufficient

Question 76

``` Is this from excessive or insufficient apoptosis: neurodegenerative diseases infection (AIDS) Ischemia Autoimmune disease (T1 diabetes) ```

Answer 76

excessive

Question 77

Cancer cells have defects in regulatory circuits that govern normal cell proliferation and apoptosis, therefore apoptosis can be used clinically how?

Answer 77

as a therapeutic target in cancer

Question 78

Drugs or therapeutic strategies that can restore the apoptotic signaling pathways towards normality have the potential to (blank) cancer cells.

Answer 78

eliminate

Question 79

What are mechanisms by which evasion of apoptosis occurs in cancer?

Answer 79

Impaired receptor signaling pathway, defects in p53, reduced expression of caspases, increased expression of IAPs, disrupted balance of BLC2 family of proteins

Question 80

A manifestation of six essential alterations in cell physiology that collectively dictate cancer growth are...

Answer 80

sustained angiogenesis, limitless replicative potential, tissue invasion and metastasis, insensitivity to anti-growth signals, self-sufficiency in growth signals, evading apoptosis

Question 81

Humans are formed from billions of cells means that billions of cells experience (blank) every day.

Answer 81

mutations

Question 82

Why do we not all die of cancer?

Answer 82

In general, many different mutations need to accumulate in a single line of cells to cause this disease – perhaps 10 to 20 mutations.

Question 83

What would the ideal cancer be?

Answer 83

based on exact understanding of intracellular state of tumor cell, and induce apoptosis

Question 84

What is important to keep in mind about tumor cells?

Answer 84

each has own set of mutations and signaling pathway resulting from random mutations

Question 85

Cancer should be viewed as what?

Answer 85

a collection of different but related diseases, with different therapeutic needs