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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

Representative western blots of Sod-1, Sod-2, Cat, Gpx-1, Ho-1 and Nrf-2 protein level in brain of normoxia- and hyperoxia-exposed CBA/H male (A) and female (B) mice (n=3 per group). Results are presented as mean±SEM of three mice per group. Protein intensities are expressed relative to ERK content. For males: a p=0.009; b p=0.026; c p=0.042, normoxia vs. hyperoxia. For females: * p=0.011; ** p=0.008, normoxia vs. hyperoxia.
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f3-medscimonitbasicres-21-191: Representative western blots of Sod-1, Sod-2, Cat, Gpx-1, Ho-1 and Nrf-2 protein level in brain of normoxia- and hyperoxia-exposed CBA/H male (A) and female (B) mice (n=3 per group). Results are presented as mean±SEM of three mice per group. Protein intensities are expressed relative to ERK content. For males: a p=0.009; b p=0.026; c p=0.042, normoxia vs. hyperoxia. For females: * p=0.011; ** p=0.008, normoxia vs. hyperoxia.

Mentions: In order to investigate antioxidative enzyme defences in response to hyperoxia, the enzymatic activities of Sod-1, Sod-2, Cat, and Gpx-1 were measured in brain of CBA/H mice of both sexes (Table 2). We found no change in activities upon treatment of neither Sod isoforms. The only change observed was the initial lower activity of Sod-1 in normoxia females compared to normoxia males (p=0.040). Considering Cat and Gpx-1 activities, while Cat activity remained unchanged irrespective of sex or treatment, slight increase in Gpx-1 activity was observed in hyperoxia-treated, compared to normoxia-treated females (p=0.04). These results suggest the absence of oxidative stress or adaptive response upon oxidative insult. Real-time PCR analysis of relative Sod-1, Sod-2, Cat, Gpx-1, Ho-1 and Nrf-2 gene expression in the brain of mice subjected to hyperoxia is shown in Figure 2. In males only Nrf-2 showed slight, but significant downregulation in hyperoxia-treated group (fold-change −1.101, p=0.001), while none of the antioxidative genes changed their expression after hyperoxia treatment (Figure 2A). In females, hyperoxia significantly upregulated Sod-1 (fold-change 1.296, p=0.046), Ho-1 (fold-change 1.232, p=0.014), and Nrf-2 (fold-change 1.167, p=0.023). Sod-2, Cat and Gpx-1 gene expression remained unchanged in these samples (Figure 2B). Western blot analysis of Sod-1, Sod-2, Cat, Gpx-1, Ho-1 and Nrf-2 protein expression in the brain of mice subjected to hyperoxia is shown on Figure 3A for males and Figure 3B for females. The level of Sod-1 protein was upregulated in both sexes (a p=0.009 for males, * p=0.011 for females) in hyperoxia treated samples, when compared to control. Contrary to Sod-1, Sod-2 protein was consistently upregulated in female brain after hyperoxia while at the same time remained unchanged in males (** p=0.008). The expression of Cat protein was increased in hyperoxia-exposed males, compared to their corresponding control (b p=0.026), while in females there was no change in protein expression upon hyperoxia. The expression of Gpx-1 protein was unchanged after hyperoxia in both sexes. Hyperoxia significantly upregulated Ho-1 protein only in males after hyperoxia treatment (c p=0.042). In females we noticed small trend for upregulation although insufficient for reaching level of statistical significance. At the same time, Nrf-2 protein remained unchanged in both sexes.


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)

Representative western blots of Sod-1, Sod-2, Cat, Gpx-1, Ho-1 and Nrf-2 protein level in brain of normoxia- and hyperoxia-exposed CBA/H male (A) and female (B) mice (n=3 per group). Results are presented as mean±SEM of three mice per group. Protein intensities are expressed relative to ERK content. For males: a p=0.009; b p=0.026; c p=0.042, normoxia vs. hyperoxia. For females: * p=0.011; ** p=0.008, normoxia vs. hyperoxia.
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f3-medscimonitbasicres-21-191: Representative western blots of Sod-1, Sod-2, Cat, Gpx-1, Ho-1 and Nrf-2 protein level in brain of normoxia- and hyperoxia-exposed CBA/H male (A) and female (B) mice (n=3 per group). Results are presented as mean±SEM of three mice per group. Protein intensities are expressed relative to ERK content. For males: a p=0.009; b p=0.026; c p=0.042, normoxia vs. hyperoxia. For females: * p=0.011; ** p=0.008, normoxia vs. hyperoxia.
Mentions: In order to investigate antioxidative enzyme defences in response to hyperoxia, the enzymatic activities of Sod-1, Sod-2, Cat, and Gpx-1 were measured in brain of CBA/H mice of both sexes (Table 2). We found no change in activities upon treatment of neither Sod isoforms. The only change observed was the initial lower activity of Sod-1 in normoxia females compared to normoxia males (p=0.040). Considering Cat and Gpx-1 activities, while Cat activity remained unchanged irrespective of sex or treatment, slight increase in Gpx-1 activity was observed in hyperoxia-treated, compared to normoxia-treated females (p=0.04). These results suggest the absence of oxidative stress or adaptive response upon oxidative insult. Real-time PCR analysis of relative Sod-1, Sod-2, Cat, Gpx-1, Ho-1 and Nrf-2 gene expression in the brain of mice subjected to hyperoxia is shown in Figure 2. In males only Nrf-2 showed slight, but significant downregulation in hyperoxia-treated group (fold-change −1.101, p=0.001), while none of the antioxidative genes changed their expression after hyperoxia treatment (Figure 2A). In females, hyperoxia significantly upregulated Sod-1 (fold-change 1.296, p=0.046), Ho-1 (fold-change 1.232, p=0.014), and Nrf-2 (fold-change 1.167, p=0.023). Sod-2, Cat and Gpx-1 gene expression remained unchanged in these samples (Figure 2B). Western blot analysis of Sod-1, Sod-2, Cat, Gpx-1, Ho-1 and Nrf-2 protein expression in the brain of mice subjected to hyperoxia is shown on Figure 3A for males and Figure 3B for females. The level of Sod-1 protein was upregulated in both sexes (a p=0.009 for males, * p=0.011 for females) in hyperoxia treated samples, when compared to control. Contrary to Sod-1, Sod-2 protein was consistently upregulated in female brain after hyperoxia while at the same time remained unchanged in males (** p=0.008). The expression of Cat protein was increased in hyperoxia-exposed males, compared to their corresponding control (b p=0.026), while in females there was no change in protein expression upon hyperoxia. The expression of Gpx-1 protein was unchanged after hyperoxia in both sexes. Hyperoxia significantly upregulated Ho-1 protein only in males after hyperoxia treatment (c p=0.042). In females we noticed small trend for upregulation although insufficient for reaching level of statistical significance. At the same time, Nrf-2 protein remained unchanged in both sexes.

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