HAL Id: hal-01163757
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01163757
Submitted on 19 Nov 2015
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Benzo[a]pyrene-induced nitric oxide production acts as a survival signal targeting mitochondrial membrane
potential
Kevin Hardonnière, Laurence Huc, Normand Podechard, Morgane Fernier, Xavier Tekpli, Isabelle Gallais, Odile Sergent, Dominique Lagadic-Gossmann
To cite this version:
Kevin Hardonnière, Laurence Huc, Normand Podechard, Morgane Fernier, Xavier Tekpli, et al..
Benzo[a]pyrene-induced nitric oxide production acts as a survival signal targeting mitochondrial mem- brane potential. Toxicology in Vitro, Elsevier, 2015, 29 (7), pp.1597-1608. �10.1016/j.tiv.2015.06.010�.
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24h 48h 72h
DAF-FM
control
a -NF 10 µM
Pifithrin α 10 µM
Figure 1
Figure 1
Figure 2
control
48h
α -NF 10 µM
DMSO B[a]P 50 nM
CH 10 µM
B
control
PIF 10 µM
control
Car 10 µM
C
control
DMSO B[a]P 50 nM DMSO B[a]P 50 nM
24h
48h
A
48h
Figure 2
Figure 3
A B
C D
DMSO B[a]P 50 nM
Vehicle SNAP
DMSO B[a]P 50 nM 0
10 20 30 40
% of cell with fragmented DNA
B[a]P 50 nM
Vehicle
LNMMA CPTIO
DMSO B[a]P 50 nM 0
10 20 30 40 50
% of cell with fragmented DNA
DMSO B[a]P 50 nM 0
50 100 150
Intracellular ATP level
B[a]P 50 nM
Vehicle LNMMA
Carboxy PTIO
***
* ***
***
DMSO B[a]P 50 nM 0
200 400 600 800 1000
DEVDase Activity RFU / µg prot
B[a]P 50 nM
Vehicle
LNNMA
CPTIO
Figure 3Figure 4
Control PIF CPTIO SNAP
CYP 1B1 D BP
50BP
1000D BP
50D BP
50D BP
50HSC 70
0 5 10 15 20 25 30 35 40
Control BP 50 BP 1000
Control BP 50 Control BP 50 Control BP 50 Control BP 50
Vehicle CH PIF CPTIO SNAP
C Y P 1 B 1 m R N A f o ld e x p re s s io n
0 5 10 15 20 25 30 35 40 45 50
Control BP 50 BP 1000
Control BP 50 Control BP 50 Control BP 50 Control BP 50
Vehicle CH PIF CPTIO SNAP
C Y P 1 B 1 m R N A f o ld e x p re s s io n
24h
48h
48h
A
B
***
***
*** ***
P<0.01
***
***
***
***
*** ***
P<0.05
* *** ***
***
P<0.001 P<0.01
P<0.01
P<0.001 P<0.01
P<0.001
Figure 4Figure 5
Control CPTIO SNAP D BP
50BP
1000D BP
50D BP
50HSC 70 p21 Control PIF
D BP
50BP
1000D BP
5024h
A
B
48h 24h
*
P<0.05 P<0.05
Figure 5
Figure 6
DiOC 6
control
a -NF 10 µM
CH223191 10 µM
A
B
Cariporide 10 µM
Pifithrin α 10 µM
control
CPTIO 25 µM
C
Figure 6
Apoptosis
B[a]P
DNA damage
NHE1 activation AhR activation
iNOS-dependent NO production
-DY m
metabolism via CYP1B1 AhR
activation
p53 activation
Figure 7
Membrane remodeling
ROS
Figure 7
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