anti-inflammatory Nrf2

Question 1

what is Nrf2 the interface of

Answer 1

redox homeostasis and intermediary metabolism

Question 2

what are the main sections of glucose homeostasis

Answer 2

glutathione and thioredoxin biosynthesis and utilization and NADPH regeneration and utilization

Question 3

what are the main sections of intermediary metabolism

Answer 3

carbohydrate metabolism, lipid metabolism, AA metabolism and penyose phosphate pathway/nucleotide metabolism

Question 4

where does Keap1 bind to

Answer 4

the N-terminal domain on Nrf2

Question 5

what does Keap1 do

Answer 5

represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain

Question 6

what does Keap1 catalyse

Answer 6

ubiquitination of Nrf2

Question 7

what do electrophilic inducers do

Answer 7

disrupt the Keap1 cycle by modifying sensor cysteines of Keap1, preventing Nrf2 ubiquitination and Keap1 regeneration

Question 8

what happens to Keap1 when electrophilic inducers are active

Answer 8

they accumulate and translocate to the nucleus

Question 9

what is the cysteine-based sensor Keap1

Answer 9

a dimer of Keap1

Question 10

how does EGFP-Keap1 degenerate

Answer 10

very efficiently

Question 11

how does Nrf2-mCherry degenerate

Answer 11

not so efficiently

Question 12

what is sulforaphane

Answer 12

an inducer of Nrf2

Question 13

where does sulforaphane work on Nrf2

Answer 13

it reacts with cysteines in Nrf2

Question 14

where is NQO1 found

Answer 14

tree bark

Question 15

what does Nrf2 act as a suppressor of

Answer 15

pro-inflammatory responses and skin carcinogenesis

Question 16

what causes skin inflammation

Answer 16

exposure to SSUV radiation

Question 17

what protects against SSUV radiation-mediated inflammation

Answer 17

genetic activation of Nrf2

Question 18

what does chronic exposure to SSUV radiation cause in mice

Answer 18

formation of tumours in SKH-1 hairless mice (which closely resemble histologically human cutaneous squamous cell carcinoma)

Question 19

what is the median rate of point mutations in SNPs (single nucleotide polymorphisms)

Answer 19

7699 per case

Question 20

what percentage if C.G - T.A base pair transitions follow a pyrimidine base to dipyrimidine oncogenic photoproducts

Answer 20

81.6%

Question 21

how is Nrf2 pharmacologically activated

Answer 21

by TBE-31

Question 22

what is azathioprine and what does it do

Answer 22

an immunosuppressive drug which aids in organ transplants

Question 23

what protects against SSUV radiation-mediated skin carcinogenesis

Answer 23

genetic activation of Nrf2 by lowering the expression of Keap1 (Keap1-KD)

Question 24

what happens in Nrf2-deficient mice

Answer 24

the protective effects of loweing the expression of Keap1 is lost

Question 25

what linerally correlates with the inhibition of pro-inflammatory responses

Answer 25

pharmacological Nrf2 activation

Question 26

what protects against SSUV radiation-mediated inflammation and skin carcinogenesis in mice

Answer 26

pharmacological or genetic nrf2 activation

Question 27

what is itaconate

Answer 27

an anti-inflammatory metabolite and an endogenous Nrf2 activator

Question 28

what causes the accumulation of itaconate

Answer 28

LPS stimulation of macrophages

Question 29

what is itaconate a product of

Answer 29

the TCA cycle

Question 30

what is itaconate involved in

Answer 30

it is weakly electrophilic and is involved in LPS-mediated stabilization of Nrf2

Question 31

what is a sensor for 4-octyl itaconate

Answer 31

C151 in Keap1

Question 32

how does itanocate activate Nrf2

Answer 32

via alkylation of Keap1

Question 33

what does Nrf2 activation potentiate

Answer 33

macrophage responses to LPS, favouring pathogen inactivation/clearance whilst attenuating IL1B pro-inflammatory signalling

Question 34

what is 4-octyl itaconate and what does it atcivate

Answer 34

a cell permeable analog of endogenous metabolite itaconate which activates Nrf2

Question 35

how does 4-octyl itaconate activate Nrf2

Answer 35

it causes 2,3-dicarbocypropylation of Keap1

Question 36

where are Nrf2-target genes suppressed

Answer 36

in COVID-19 patient biopsies

Question 37

what counteracts SARS-CoV2 infection

Answer 37

4-octyl itaconate

Question 38

wich type of cells have a low transition probability into later stages of HSV1 infection

Answer 38

cells with a high level if transcripts of Nrf2-target genes, and therefore high Nrf2 activity

Question 39

what do cells at later stages of infection respond by doing

Answer 39

increasing transcription of Nrf2-target genes

Question 40

what does increasing transcription of Nrf2-target genes do

Answer 40

could reflect a cellular defense mechanism against HSV1 infection

Question 41

what counteracts HSV1 infection

Answer 41

pharmacological activation of Nrf2 with bardoxolone methyl or sulforaphane

Question 42

what happens when viruses (such as HSV1 and SARS-CoV2) inactive Nrf2

Answer 42

they use this as a mechanism to enhance their own propagation