Which outcome most likely results from exposure of Ogg1 mice to TNFa O A. Increase in cancer incidence O B. Increase in Cxc/1 expression O C. Decrease in cellular ROS levels O D. Decrease in Kp of TH5487 for its target TH5487 acts as which type of inhibitor? O A. Competitive OB. Mixed O C. Noncompetitive O D. Uncompetitive Based on data shown in Figure 2, what are the effects of OGG1 and TH5487 on Cxc/1 expression? I. OGG1 reduces the TNFa induced Cxc/1 expression. II. OGG1 stimulates the TNFa induced Cxc/1 expression. III. TH5487 reduces the OGG1-mediated Cxc/1 expression. IV. TH5487 stimulates the OGG1-mediated Cxc/1 expression. O A. I and III only OB. I and IV only O C. II and III only O D. II and IV only Researchers measured the NF- KB occupancy of the Cxc/2 promoter following exposure to TNFa both in the presence and absence of TH5487. Based on the data. presented in the passage, which figure depicts the expected results? TNFα: TH5487: II LI TNFa: TH5487: + + O A. O B. O C. O D. NF-KB occupancy NF-KB occupancy L.I. NF-KB occupancy TNFa: TH5487: NF-KB occupancy + L... TNFα: TH5487: + + + + + +
Which outcome most likely results from exposure of Ogg1 mice to TNFa O A. Increase in cancer incidence O B. Increase in Cxc/1 expression O C. Decrease in cellular ROS levels O D. Decrease in Kp of TH5487 for its target TH5487 acts as which type of inhibitor? O A. Competitive OB. Mixed O C. Noncompetitive O D. Uncompetitive Based on data shown in Figure 2, what are the effects of OGG1 and TH5487 on Cxc/1 expression? I. OGG1 reduces the TNFa induced Cxc/1 expression. II. OGG1 stimulates the TNFa induced Cxc/1 expression. III. TH5487 reduces the OGG1-mediated Cxc/1 expression. IV. TH5487 stimulates the OGG1-mediated Cxc/1 expression. O A. I and III only OB. I and IV only O C. II and III only O D. II and IV only Researchers measured the NF- KB occupancy of the Cxc/2 promoter following exposure to TNFa both in the presence and absence of TH5487. Based on the data. presented in the passage, which figure depicts the expected results? TNFα: TH5487: II LI TNFa: TH5487: + + O A. O B. O C. O D. NF-KB occupancy NF-KB occupancy L.I. NF-KB occupancy TNFa: TH5487: NF-KB occupancy + L... TNFα: TH5487: + + + + + +
Biochemistry
9th Edition
ISBN:9781319114671
Author:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Publisher:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Chapter1: Biochemistry: An Evolving Science
Section: Chapter Questions
Problem 1P
Related questions
Question
Transcribed Image Text:Which outcome most likely results from exposure of
Ogg1 mice to TNFa
O A.
Increase in cancer incidence.
O B. Increase in Cxc/1 expression
O C. Decrease in cellular ROS levels
O D. Decrease in Kp of TH5487 for its target
TH5487 acts as which type of inhibitor?
O A. Competitive
O B. Mixed
O C. Noncompetitive
O D. Uncompetitive
Based on data shown in Figure 2, what are the effects of
OGG1 and TH5487 on Cxc/1 expression?
I. OGG1 reduces the TNFA induced Cxc/1 expression.
II. OGG1 stimulates the TNFa induced Cxc/1
expression.
III. TH5487 reduces the OGG1-mediated Cxc/1
expression.
IV. TH5487 stimulates the OGG1-mediated Cxc/1
expression.
O A. I and III only
O B. I and IV only
OC. II and III only.
O D. II and IV only
Researchers measured the NF- KB occupancy of the
Cxcl2 promoter following exposure to TNFa both in the
presence and absence of TH5487. Based on the data
presented in the passage, which figure depicts the
expected results?
O A.
OB.
O C.
COD.
NF-KB occupancy
TNFa:
TH5487:
NF-KB occupancy
TNFa:
TH5487:
NF-KB occupancy
TNFa:
TH5487:
NF-KB occupancy
JI
L.I.
TNFa:
TH5487:
ا..
+
+
+
+
+
+
+
+
![Upon exposure to pro-inflammatory agents such
as TNFA, cells produce reactive oxygen species
(ROS), which can react with guanine bases in DNA to
generate 8-oxo-G. This modified guanine can
participate in Hoogsteen base pairs with adenine, an
event that upon DNA replication results in G to T and
C to A mutations. Guanine-rich promoter regions are
particularly susceptible to this type of ROS-induced
DNA damage.
OGG1 is a DNA glycosylase that recognizes 8-oxo-
G. OGG1 is involved in two processes: base excision
repair of 8-oxo-G as well as transcription initiation for
pro-inflammatory genes such as Cxcl family
members. These transcription events also involve
binding of NF-KB to promoters as NF-KB recruitment
increases dramatically following OGG1 binding to
DNA.
TH5487 is a compound that mimics 8-oxo-G
structure and binds to the active site of OGG1. Using
reverse-transcription PCR (RT-PCR), researchers
examined whether increasing levels of TH5487
affected the expression of a pro-inflammatory gene
following TNFa exposure (Figure 1). Next, the
researchers exposed both wild-type and Ogg1-
knockout (Ogg1-/-) mice to TNFa in the presence and
absence of TH5487 and monitored Cxc/1 expression
levels (Figure 2).
mRNA levels (%)
Figure 1
100.
Figure 2
80-
60+
40+
20-
0
0
Cxc/1 expression
5
TNFα:
TH5487:
10
15
[TH5487] (UM)
wild-type
□Ogg1-/-
0.
Effect of TH5487 on pro-inflammatory
gene expression levels following
exposure to TNFa
20
Cxc/1 expression levels for wild-type and
Ogg1- mice in the presence (+) and
absence (-) of TNFa and TH5487](/v2/_next/image?url=https%3A%2F%2Fcontent.bartleby.com%2Fqna-images%2Fquestion%2F8632ab95-12c0-43a1-a9c9-ae2ef8531ad4%2F484f7fa4-bda2-40c8-a400-0342072a5e7b%2Ffeo7ike_processed.jpeg&w=3840&q=75)
Transcribed Image Text:Upon exposure to pro-inflammatory agents such
as TNFA, cells produce reactive oxygen species
(ROS), which can react with guanine bases in DNA to
generate 8-oxo-G. This modified guanine can
participate in Hoogsteen base pairs with adenine, an
event that upon DNA replication results in G to T and
C to A mutations. Guanine-rich promoter regions are
particularly susceptible to this type of ROS-induced
DNA damage.
OGG1 is a DNA glycosylase that recognizes 8-oxo-
G. OGG1 is involved in two processes: base excision
repair of 8-oxo-G as well as transcription initiation for
pro-inflammatory genes such as Cxcl family
members. These transcription events also involve
binding of NF-KB to promoters as NF-KB recruitment
increases dramatically following OGG1 binding to
DNA.
TH5487 is a compound that mimics 8-oxo-G
structure and binds to the active site of OGG1. Using
reverse-transcription PCR (RT-PCR), researchers
examined whether increasing levels of TH5487
affected the expression of a pro-inflammatory gene
following TNFa exposure (Figure 1). Next, the
researchers exposed both wild-type and Ogg1-
knockout (Ogg1-/-) mice to TNFa in the presence and
absence of TH5487 and monitored Cxc/1 expression
levels (Figure 2).
mRNA levels (%)
Figure 1
100.
Figure 2
80-
60+
40+
20-
0
0
Cxc/1 expression
5
TNFα:
TH5487:
10
15
[TH5487] (UM)
wild-type
□Ogg1-/-
0.
Effect of TH5487 on pro-inflammatory
gene expression levels following
exposure to TNFa
20
Cxc/1 expression levels for wild-type and
Ogg1- mice in the presence (+) and
absence (-) of TNFa and TH5487
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