Cyp4a14 overexpression induced by hyperoxia in female CBA mice as a possible contributor of increased resistance to oxidative stress.
The beneficial effects of hyperoxia have been noted in treatment of several diseases and pathological states. However, the excessive production of ROS under hyperoxic conditions can directly damage cellular macromolecules if the imbalance in antioxidant status exists. Cytochrome P450 (Cyp) 4a14 has an important role in the metabolism of lipids and as a source of ROS in oxidative stress. This study investigated the oxidant/antioxidant status as a response to hyperoxia treatment in liver of young CBA/Hr mice of both sexes and whether the observed response is mediated by Cyp4a14 via PPAR isoforms in a sex-dependent manner. The overexpression of Cyp4a14, lack of both LPO and of 4-hydroxynonenal(HNE)-protein adducts revealed by immunohistochemical analysis in hyperoxia-treated females indicates their greater resistance to hyperoxia compared to males, which is parallelled to changes in PPARbeta/delta and PPARgamma expression. These results suggest the presence of sex-dependent changes in all investigated parameters, which points out sex-related susceptibility towards oxidative stress and hyperoxia treatment of various pathological conditions and diseases.
Sobocanec
Sandra
S
Division of Molecular Medicine, Ruder Bosković Institute, Bijenicka 54, 10000 Zagreb, Croatia. ssoboc@irb.hr
Balog
Tihomir
T
Sarić
Ana
A
Sverko
Visnja
V
Zarković
Neven
N
Gasparović
Ana Cipak
AC
Zarković
Kamelija
K
Waeg
Georg
G
Macak-Safranko
Zeljka
Z
Kusić
Borka
B
Marotti
Tanja
T
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000072470:Cytochrome P450 Family 4; D005260:Female; D018496:Hyperoxia; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D018384:Oxidative Stress; D020133:Reverse Transcriptase Polymerase Chain Reaction
C436963:Cyp4a14 protein, mouse; D003577:Cytochrome P-450 Enzyme System; D000072470:Cytochrome P450 Family 4