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Diminished Resistance to Hyperoxia in Brains of Reproductively Senescent Female CBA/H Mice.

Šarić A, Sobočanec S, Mačak Šafranko Ž, Popović Hadžija M, Bagarić R, Farkaš V, Švarc A, Marotti T, Balog T - Med Sci Monit Basic Res (2015)

Bottom Line: Expression of Nrf-2 showed significant downregulation in hyperoxia-treated males (p=0.001), and upregulation in hyperoxia-treated females (p=0.023).Uptake of 18FDG was decreased after hyperoxia in the back brain of females.CONCLUSIONS We found that females at their reproductive senescence are more susceptible to hyperoxia, compared to males.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia.

ABSTRACT
BACKGROUND We have explored sex differences in ability to maintain redox balance during acute oxidative stress in brains of mice. We aimed to determine if there were differences in oxidative/antioxidative status upon hyperoxia in brains of reproductively senescent CBA/H mice in order to elucidate some of the possible mechanisms of lifespan regulation. MATERIAL AND METHODS The brains of 12-month-old male and female CBA/H mice (n=9 per sex and treatment) subjected to 18-h hyperoxia were evaluated for lipid peroxidation (LPO), antioxidative enzyme expression and activity - superoxide dismutase 1 and 2 (Sod-1, Sod-2), catalase (Cat), glutathione peroxidase 1 (Gpx-1), heme-oxygenase 1 (Ho-1), nad NF-E2-related factor 2 (Nrf2), and for 2-deoxy-2-[18F] fluoro-D-glucose (18FDG) uptake. RESULTS No increase in LPO was observed after hyperoxia, regardless of sex. Expression of Nrf-2 showed significant downregulation in hyperoxia-treated males (p=0.001), and upregulation in hyperoxia-treated females (p=0.023). Also, in females hyperoxia upregulated Sod-1 (p=0.046), and Ho-1 (p=0.014) genes. SOD1 protein was upregulated in both sexes after hyperoxia (p=0.009 for males and p=0.011 for females). SOD2 protein was upregulated only in females (p=0.008) while CAT (p=0.026) and HO-1 (p=0.042) proteins were increased after hyperoxia only in males. Uptake of 18FDG was decreased after hyperoxia in the back brain of females. CONCLUSIONS We found that females at their reproductive senescence are more susceptible to hyperoxia, compared to males. We propose this model of hyperoxia as a useful tool to assess sex differences in adaptive response to acute stress conditions, which may be partially responsible for observed sex differences in longevity of CBA/H mice.

No MeSH data available.


Related in: MedlinePlus

Schematic diagram of the experimental groups used in this study. LPO-lipid peroxidation; AOX-antioxidative enzyme activities; RT-PCR: real-time PCR; WB-western blot.
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f1-medscimonitbasicres-21-191: Schematic diagram of the experimental groups used in this study. LPO-lipid peroxidation; AOX-antioxidative enzyme activities; RT-PCR: real-time PCR; WB-western blot.

Mentions: The experiments were performed in accordance with the current laws of the Republic of Croatia and with the guidelines of European Community Council Directive of November 24, 1986 (86/609/EEC). All applicable institutional and/or national guidelines for the care and use of animals were followed. Twelve months old male and female CBA/H mice from breeding colony of the Ruđer Bošković Institute (Zagreb, Croatia) were maintained under the following laboratory conditions: 12-h light/day cycle, 22±2°C room temperature; access to food pellets and tap water ad libitum. In this study total of 36 animals were used. Schematic diagram of the experimental groups is presented in Figure 1. Hyperoxic oxygen conditions were carried out by flushing the chamber (Đuro Đaković, Slavonski Brod, Croatia) with pure oxygen (25 L/min for 10 minutes) to replace air. Normoxic O2 conditions serving as a control were obtained by keeping mice in the same chamber, but under ambient air. The animals were divided into two groups: control (n=9), receiving normoxic oxygen (21% O2) and hyperoxia-treated (n=9), receiving pure oxygen (95% O2) for 18 hours. Two animals from each group were randomly chosen and recorded for the PET scan analysis. After the analysis, animals were euthanized by cervical dislocation. The brains from animals used in PET scan analysis were not used for other experiments. For biochemical analyses, each group consisted of seven animals. Briefly, after exposure to normoxic air/pure oxygen, mice were euthanized by cervical dislocation and brains were immediately rinsed in cold 50mM PBS (pH=7.8) and subjected to further analyses.


Diminished Resistance to Hyperoxia in Brains of Reproductively Senescent Female CBA/H Mice.

Šarić A, Sobočanec S, Mačak Šafranko Ž, Popović Hadžija M, Bagarić R, Farkaš V, Švarc A, Marotti T, Balog T - Med Sci Monit Basic Res (2015)

Schematic diagram of the experimental groups used in this study. LPO-lipid peroxidation; AOX-antioxidative enzyme activities; RT-PCR: real-time PCR; WB-western blot.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4588673&req=5

f1-medscimonitbasicres-21-191: Schematic diagram of the experimental groups used in this study. LPO-lipid peroxidation; AOX-antioxidative enzyme activities; RT-PCR: real-time PCR; WB-western blot.
Mentions: The experiments were performed in accordance with the current laws of the Republic of Croatia and with the guidelines of European Community Council Directive of November 24, 1986 (86/609/EEC). All applicable institutional and/or national guidelines for the care and use of animals were followed. Twelve months old male and female CBA/H mice from breeding colony of the Ruđer Bošković Institute (Zagreb, Croatia) were maintained under the following laboratory conditions: 12-h light/day cycle, 22±2°C room temperature; access to food pellets and tap water ad libitum. In this study total of 36 animals were used. Schematic diagram of the experimental groups is presented in Figure 1. Hyperoxic oxygen conditions were carried out by flushing the chamber (Đuro Đaković, Slavonski Brod, Croatia) with pure oxygen (25 L/min for 10 minutes) to replace air. Normoxic O2 conditions serving as a control were obtained by keeping mice in the same chamber, but under ambient air. The animals were divided into two groups: control (n=9), receiving normoxic oxygen (21% O2) and hyperoxia-treated (n=9), receiving pure oxygen (95% O2) for 18 hours. Two animals from each group were randomly chosen and recorded for the PET scan analysis. After the analysis, animals were euthanized by cervical dislocation. The brains from animals used in PET scan analysis were not used for other experiments. For biochemical analyses, each group consisted of seven animals. Briefly, after exposure to normoxic air/pure oxygen, mice were euthanized by cervical dislocation and brains were immediately rinsed in cold 50mM PBS (pH=7.8) and subjected to further analyses.

Bottom Line: Expression of Nrf-2 showed significant downregulation in hyperoxia-treated males (p=0.001), and upregulation in hyperoxia-treated females (p=0.023).Uptake of 18FDG was decreased after hyperoxia in the back brain of females.CONCLUSIONS We found that females at their reproductive senescence are more susceptible to hyperoxia, compared to males.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia.

ABSTRACT
BACKGROUND We have explored sex differences in ability to maintain redox balance during acute oxidative stress in brains of mice. We aimed to determine if there were differences in oxidative/antioxidative status upon hyperoxia in brains of reproductively senescent CBA/H mice in order to elucidate some of the possible mechanisms of lifespan regulation. MATERIAL AND METHODS The brains of 12-month-old male and female CBA/H mice (n=9 per sex and treatment) subjected to 18-h hyperoxia were evaluated for lipid peroxidation (LPO), antioxidative enzyme expression and activity - superoxide dismutase 1 and 2 (Sod-1, Sod-2), catalase (Cat), glutathione peroxidase 1 (Gpx-1), heme-oxygenase 1 (Ho-1), nad NF-E2-related factor 2 (Nrf2), and for 2-deoxy-2-[18F] fluoro-D-glucose (18FDG) uptake. RESULTS No increase in LPO was observed after hyperoxia, regardless of sex. Expression of Nrf-2 showed significant downregulation in hyperoxia-treated males (p=0.001), and upregulation in hyperoxia-treated females (p=0.023). Also, in females hyperoxia upregulated Sod-1 (p=0.046), and Ho-1 (p=0.014) genes. SOD1 protein was upregulated in both sexes after hyperoxia (p=0.009 for males and p=0.011 for females). SOD2 protein was upregulated only in females (p=0.008) while CAT (p=0.026) and HO-1 (p=0.042) proteins were increased after hyperoxia only in males. Uptake of 18FDG was decreased after hyperoxia in the back brain of females. CONCLUSIONS We found that females at their reproductive senescence are more susceptible to hyperoxia, compared to males. We propose this model of hyperoxia as a useful tool to assess sex differences in adaptive response to acute stress conditions, which may be partially responsible for observed sex differences in longevity of CBA/H mice.

No MeSH data available.


Related in: MedlinePlus