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PHYL 4504 > Oxidative Stress > Flashcards

Oxidative Stress Flashcards

1
Q

the lung has the highest exposure to what two things

A

atmospheric oxygen and environmental oxidants

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2
Q

epithelial cells are exposed to oxidants that are generated both ___ and ___

A

internally and externally

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3
Q

examples of internally generated oxidants

A

come from normal metabolic processes , O2-

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4
Q

what is an example of an externally generated oxidant

A

environmental pollutants

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5
Q

airways possess antioxidants that are _____ and ___

A

non enzymatic and enzymatic

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6
Q

examples of non enzymatic antioxidants

A

glutathione, vitamin C, vitamin E, beta carotene, uric acid

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7
Q

examples of enzymatic antioxidants

A

superoxide dismutases, catalases, and peroxidases

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8
Q

oxidative stress has been implacted in the pathogenesis and progression of many ____

A

pulmonary diseases such as asthma, CF, COPD

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9
Q

name 2 sources of oxidants in the lung

A

environmental factors and endogenous species

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10
Q

what are some environmental factors of oxidants

A

ozone, air pollution, particulates containing metals and cigarette smoke

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11
Q

what are some examples of endogenous oxidants

A

by products of mitochondrial respiration and inflammatory cell products

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12
Q

the redox status of the lung is ___ not ____

A

reducing not oxidizing

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13
Q

the vast excess of ___ substances over ___ ones is maintained by a rich array of antioxidant enzymes and nonenzymatic effectors on the surface and within epithilial cells

A

reduced, oxidized

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14
Q

Normally there is enough ___ in the body to counter the production of a small amount of ROS

A

antioxidants

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15
Q

if the levels of antioxidants are ____ or the production of ROS ____ the balance is tippes toward oxidative stress

A

diminished, increased

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16
Q

what is a free radical

A

any species that contains one or more unpaied electrons

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17
Q

some examples of a free radical

A

superoxide anion, hydroxyl radical

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18
Q

what are some examples of non radical reactive species

A

NO, and H2O2

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19
Q

What is the ultimate ROS that leads to cell damage

A

hydrogen peroxide

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20
Q

primary ROS production in vivo are

A

O2- and H2O2

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21
Q

most harmful ROS is

A

OH with an electron

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22
Q

cellular sources of ROS in the lung

A

neutrophils, eosinophils, alveolar macrophages, alveolar and bronchial epithelial cells, endothelial cells

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23
Q

exogenous sources of ROS

A

exposure to chemical agemts like mineral dust, ozone, nitrogen oxides, ionizing radiation, cigarette smoke

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24
Q

oxidant stress results in

A

peroxidation of membrane lipids, depletion of nucleotides, rises in intracellular calcium, cytoskeletal distruption, NDA damage and chanes in ion channel functioning

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25
Q

what do antioxidants do to oxdiants

A

neutralize them

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26
Q

what turns superoxide aniton and 2 H+ into H2O2 and O2

A

superoxide dismutase

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27
Q

what urns 2 H2O2 into O2 and 2 H2O

A

catalase

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28
Q

glutahtione is a tripeptide composed of

A

glutamic acid, cysteine and glycine

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29
Q

what is the mian funcitonal element of glutathione

A

cysteine

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30
Q

what reactive gorup does the cysteine contain

A

thiol group

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31
Q

what reduced H2O2 to H2O

A

glutathione peroxidase

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32
Q

Ratio of ___:____ is an important marker of redox status

A

GSH:GSSG

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33
Q

glutathione reduced form

A

GSH

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34
Q

glutathione oxidized form

A

GSSG

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35
Q

what kind of antioxidant is superoxide dismutase

A

enzymatic

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36
Q

what are the three types of SODs

A

copper, zinc
manganese
extracellular

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37
Q

what reaction does SOD catalyze

A

2O2- and 2H+ into H2O2 and O2

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38
Q

copper and zinc SOD is _______ in ciliated bronchial epithelial cells

A

constitutively expressed

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39
Q

what SOD is decreased in asthmatic airways

A

copper zinc SOD

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40
Q

MnSOD is inducible by

A

cytokines, cigarette smoke and hyperoxia

41
Q

knockout ____ mice are lethal

A

MnSOD

42
Q

extracellular SOD requires

A

Zn and Cu

43
Q

ECSOD regulates ___ levels

A

NO

44
Q

there are high levels of ECSOD in ______

A

ECM

45
Q

what is the first line of defence against inhaled oxidants

A

ECSOD (and glutathione perioxidase)

46
Q

what does catalse do?

A

decomposes hydrogen peroxide into water

47
Q

___ is ubiquitous but concentrated in the liver and RBC

A

catalase

48
Q

some studies report catalse is induced by

A

hyperoxia, oxidants and some cytokines

49
Q

Glutathione peroxidase reduces ___ to ____ by ____

A

H2O2 to H2O , oxydizing glutathione

50
Q

write the reaction for glutathione peroxidase

A

H2O2 + 2GSH –> GSSG + 2H2H

51
Q

reduction of GSSG os catalysed by

A

glutathione reductase

52
Q

what is the cosubstrate of glutathione reductase

A

NADPH

53
Q

what cycle is essential to antioxidant defence of the cell?

A

GSH cycle

54
Q

what do all four described Gpx contain in their active site

A

selenium atom

55
Q

what has very high amounts of glutathione peroxidase and GSH

A

alveolar epithelial lining fluid

56
Q

heme oxygenase (HO) catalyses degradation of ___ into ___ which releases ____ and ___

A

heme into bile pigment biliverdin, CO and Fe2+

57
Q

billiverdin is transofrmed into ____

A

billirubin

58
Q

Fe2+ can be bound to iron storage protein ___

A

ferritin

59
Q

what is HO induced by

A

hyperoxia and hypozia, LPS and oxidative stress

60
Q

CO is a good ____ agent

A

antiinflammatory

61
Q

what is induced in pulmonary diseases associated with O.S

A

HO-1

62
Q

samples from CF patients show rncreased ___ expression

A

HO-1

63
Q

Thioredoxins are ____ disulphide reductases belonging to what family

A

ubiquitous , flavoprotein

64
Q

what do thoredozins do?

A

maintain proteins in reduced state

65
Q

how do thioredoxins work

A

by catalyzing reduction of disulphise to sulfhydryls

66
Q

thioredoxins and thioredoxin reductases work together and require reduced ___ for their function

A

NADPH

67
Q

reactive nitrogen species examples

A

nitric oxide, peroxynitrite, nitrogen dioxide

68
Q

NO can react with ____ to form other reactive species

A

ROS

69
Q

what is essential for killing invading microorganisms

A

RNS

70
Q

what are the deleterious effects of RNS

A

damage to DNA, lipids, proteins and carbs resulting in impaired cellular function and enhanced inflammatory reactions

71
Q

nitrogen species result in nitration of ___ residues

A

tyrosine

72
Q

RNS associated with

A

asthma, COPD, CF, ARDS, interstitial pulmonary fibrosis

73
Q

increase production of ____ in the presence of oxidative stress leads to production of strong oxidants

A

NO

74
Q

MPO and EPO catalyse oxidation of ____ by H2O2 to form _____

A

halides, hypohalous acids

75
Q

NO is produced by

A

nitric oxide synthase

76
Q

what are the three isoforms of NOS

A

neuronal, indicuble and endothelial

77
Q

which NOS increases in inflammatory lung diseases

A

inducible NOS

78
Q

there is ___ levels of NO echaled by asthmatics

A

increased

79
Q

what can supress iNOS expression and exhalation of NO in asthma

A

steorids

80
Q

there is ____ between ROS and RNS in pathogenesis of inflammatory lung disease

A

cross talk

81
Q

what is reduced in epithlial lining fluid of CF compared to control

A

GSD = glutathione

82
Q

CF lung disease is characterized by ____ dominated airway inflammation

A

neutrophil

83
Q

CF lungs have ______ oxidant production

A

increased

84
Q

poor nutritional status of CF so they lack ____

A

dietary antioxidants

85
Q

CFTR channel can transport ____, so CF patients have less of this in their PCL

A

GSH

86
Q

CFTR mediated GSH transport may serve to ____ mucous viscocity by ______

A

reduce, disrupting disulphide bond formaiton in mucin proteins

87
Q

decrease in antioxidants plus increase in ROS =

A

double whammy of oxidative stress

88
Q

what is asthma

A

chronic inflammatory disease of lower airways

89
Q

what is asthma caracterized by

A

reversible airway obstruction and hyperresponsiveness

90
Q

what is increase in asthma

A

ROS and RNS

91
Q

what levels are increase in BAL of asthmatics

A

EOP and MOP

92
Q

what appears to contribute to airway remodeling in asthma

A

peroxynitrite

93
Q

inflammaotry cells in asthmatic produced more ___ when compared with controls

A

ROS

94
Q

asthma attacks are associated with immediate formaiton of

A

O2-

95
Q

deficiency of ___ in asthma

A

SOD

96
Q

apoptosis and ___ are seen in asthmatic patients

A

shedding of epithelial cells

97
Q

exposure to ROS and RNS leads to ____

A

extrusion of intracellular GSH/GSSG

98
Q

loss of SOD activity and GSH extrusion activates

A

BAX and caspases, triggering cytocrhome p release form mitochondria and entry into apoptosis

PHYL 4504 (8 decks)

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