Oxidative Stress Flashcards

(98 cards)

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
what do antioxidants do to oxdiants
neutralize them
26
what turns superoxide aniton and 2 H+ into H2O2 and O2
superoxide dismutase
27
what urns 2 H2O2 into O2 and 2 H2O
catalase
28
glutahtione is a tripeptide composed of
glutamic acid, cysteine and glycine
29
what is the mian funcitonal element of glutathione
cysteine
30
what reactive gorup does the cysteine contain
thiol group
31
what reduced H2O2 to H2O
glutathione peroxidase
32
Ratio of ___:____ is an important marker of redox status
GSH:GSSG
33
glutathione reduced form
GSH
34
glutathione oxidized form
GSSG
35
what kind of antioxidant is superoxide dismutase
enzymatic
36
what are the three types of SODs
copper, zinc manganese extracellular
37
what reaction does SOD catalyze
2O2- and 2H+ into H2O2 and O2
38
copper and zinc SOD is _______ in ciliated bronchial epithelial cells
constitutively expressed
39
what SOD is decreased in asthmatic airways
copper zinc SOD
40
MnSOD is inducible by
cytokines, cigarette smoke and hyperoxia
41
knockout ____ mice are lethal
MnSOD
42
extracellular SOD requires
Zn and Cu
43
ECSOD regulates ___ levels
NO
44
there are high levels of ECSOD in ______
ECM
45
what is the first line of defence against inhaled oxidants
ECSOD (and glutathione perioxidase)
46
what does catalse do?
decomposes hydrogen peroxide into water
47
___ is ubiquitous but concentrated in the liver and RBC
catalase
48
some studies report catalse is induced by
hyperoxia, oxidants and some cytokines
49
Glutathione peroxidase reduces ___ to ____ by ____
H2O2 to H2O , oxydizing glutathione
50
write the reaction for glutathione peroxidase
H2O2 + 2GSH --> GSSG + 2H2H
51
reduction of GSSG os catalysed by
glutathione reductase
52
what is the cosubstrate of glutathione reductase
NADPH
53
what cycle is essential to antioxidant defence of the cell?
GSH cycle
54
what do all four described Gpx contain in their active site
selenium atom
55
what has very high amounts of glutathione peroxidase and GSH
alveolar epithelial lining fluid
56
heme oxygenase (HO) catalyses degradation of ___ into ___ which releases ____ and ___
heme into bile pigment biliverdin, CO and Fe2+
57
billiverdin is transofrmed into ____
billirubin
58
Fe2+ can be bound to iron storage protein ___
ferritin
59
what is HO induced by
hyperoxia and hypozia, LPS and oxidative stress
60
CO is a good ____ agent
antiinflammatory
61
what is induced in pulmonary diseases associated with O.S
HO-1
62
samples from CF patients show rncreased ___ expression
HO-1
63
Thioredoxins are ____ disulphide reductases belonging to what family
ubiquitous , flavoprotein
64
what do thoredozins do?
maintain proteins in reduced state
65
how do thioredoxins work
by catalyzing reduction of disulphise to sulfhydryls
66
thioredoxins and thioredoxin reductases work together and require reduced ___ for their function
NADPH
67
reactive nitrogen species examples
nitric oxide, peroxynitrite, nitrogen dioxide
68
NO can react with ____ to form other reactive species
ROS
69
what is essential for killing invading microorganisms
RNS
70
what are the deleterious effects of RNS
damage to DNA, lipids, proteins and carbs resulting in impaired cellular function and enhanced inflammatory reactions
71
nitrogen species result in nitration of ___ residues
tyrosine
72
RNS associated with
asthma, COPD, CF, ARDS, interstitial pulmonary fibrosis
73
increase production of ____ in the presence of oxidative stress leads to production of strong oxidants
NO
74
MPO and EPO catalyse oxidation of ____ by H2O2 to form _____
halides, hypohalous acids
75
NO is produced by
nitric oxide synthase
76
what are the three isoforms of NOS
neuronal, indicuble and endothelial
77
which NOS increases in inflammatory lung diseases
inducible NOS
78
there is ___ levels of NO echaled by asthmatics
increased
79
what can supress iNOS expression and exhalation of NO in asthma
steorids
80
there is ____ between ROS and RNS in pathogenesis of inflammatory lung disease
cross talk
81
what is reduced in epithlial lining fluid of CF compared to control
GSD = glutathione
82
CF lung disease is characterized by ____ dominated airway inflammation
neutrophil
83
CF lungs have ______ oxidant production
increased
84
poor nutritional status of CF so they lack ____
dietary antioxidants
85
CFTR channel can transport ____, so CF patients have less of this in their PCL
GSH
86
CFTR mediated GSH transport may serve to ____ mucous viscocity by ______
reduce, disrupting disulphide bond formaiton in mucin proteins
87
decrease in antioxidants plus increase in ROS =
double whammy of oxidative stress
88
what is asthma
chronic inflammatory disease of lower airways
89
what is asthma caracterized by
reversible airway obstruction and hyperresponsiveness
90
what is increase in asthma
ROS and RNS
91
what levels are increase in BAL of asthmatics
EOP and MOP
92
what appears to contribute to airway remodeling in asthma
peroxynitrite
93
inflammaotry cells in asthmatic produced more ___ when compared with controls
ROS
94
asthma attacks are associated with immediate formaiton of
O2-
95
deficiency of ___ in asthma
SOD
96
apoptosis and ___ are seen in asthmatic patients
shedding of epithelial cells
97
exposure to ROS and RNS leads to ____
extrusion of intracellular GSH/GSSG
98
loss of SOD activity and GSH extrusion activates
BAX and caspases, triggering cytocrhome p release form mitochondria and entry into apoptosis