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Tert-buthylhydroquinone pre-conditioning exerts dual effects in old female rats exposed to 3-nitropropionic acid

View Article: PubMed Central - PubMed

ABSTRACT

The brain is a very susceptible organ to structural and functional alterations caused by oxidative stress and its vulnerability increases with age. Understanding the antioxidant response activated by the transcription factor Nrf2 has become very important in the aging field in order to activate cellular protection. However, the role of Nrf2 inducers during old age has not been completely understood. Our aim was to activate the Nrf2 pathway by pre-treating old rats with a widely used Nrf2-inducer, tert-buthylhydroquinone (tBHQ), prior to 3-nitropropionic acid (3-NP) insult, in order to evaluate its effects at a behavioral, morphological and biochemical levels. 3-NP has been used to reproduce the biochemical and pathophysiological characteristics of Huntington's disease due to an oxidative effect. Our results suggest that tBHQ confers an important protective effect against 3-NP toxicity; nevertheless, Nrf2 seems not to be the main protective pathway associated to neuroprotection. Hormetic responses include the activation of more than one transcription factor. Nrf2 and NFκB are known to simultaneously initiate different cellular responses against stress by triggering parallel mechanisms, therefore NFκB nuclear accumulation was also evaluated.

No MeSH data available.


Nrf2 nuclear and cytosolic levels. A. Representative images of Nrf2 nuclear accumulation (Nuc Frac) in adult and old animals after tBHQ PreT and densitometric analysis. For Adult, ap<0.05,bp<0.01 vs Ct, cp<0.001 vs 3-NP. For Old, ap<0.01 vs Ct, bp<0.05 vs 3-NP. B. Representative images of Nrf2 content in the cytosolic fraction (Cyt Frac) in adult and old animals and densitometric analysis. ap<0.01 vs Ct, bp<0.05 vs 3NP. C. Representative images of antioxidant enzymes regulated by Nrf2 evaluated in the Cyt Frac in adult and old animals and densitometric analysis. ap<0.001, bp<0.05 vs Ct, cp<0.001,dp<0.05 vs 3-NP. Similar results were obtained from three independent experiments. All data are represented as mean±SD (n=3 in each group).
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f0030: Nrf2 nuclear and cytosolic levels. A. Representative images of Nrf2 nuclear accumulation (Nuc Frac) in adult and old animals after tBHQ PreT and densitometric analysis. For Adult, ap<0.05,bp<0.01 vs Ct, cp<0.001 vs 3-NP. For Old, ap<0.01 vs Ct, bp<0.05 vs 3-NP. B. Representative images of Nrf2 content in the cytosolic fraction (Cyt Frac) in adult and old animals and densitometric analysis. ap<0.01 vs Ct, bp<0.05 vs 3NP. C. Representative images of antioxidant enzymes regulated by Nrf2 evaluated in the Cyt Frac in adult and old animals and densitometric analysis. ap<0.001, bp<0.05 vs Ct, cp<0.001,dp<0.05 vs 3-NP. Similar results were obtained from three independent experiments. All data are represented as mean±SD (n=3 in each group).

Mentions: Nrf2 distribution in nuclear and cytosolic fractions was evaluated in the brains from old and adult treated animals. Differential effects in both age groups were observed (Fig. 6A). The old animals slightly increased Nrf2 nuclear translocation with tBHQ while in increased Nrf2 was found in the nuclear fraction of adult animals treated with 3-NP alone, (p<0.01) when compared to the control, tBHQ and PreT treated animals. In contrast, nuclear Nrf2 accumulation in old animals was only observed (10%, p<0.01) in tBHQ treated rats. Both animal groups, adult and old, decreased Nrf2 nuclear accumulation after tBHQ PreT (Fig. 6A). On the contrary, tBHQ PreT induced a greater cytoplasmic Nrf2 accumulation in adult animals (60%, p<0.01), while in old animals Nrf2 levels decreased (p<0.05) compared to the 3-NP group, which did not modify the Nrf2 cytosolic content (Fig. 6B). Our data indicate that Nrf2 is not efficiently translocated to the nucleus after tBHQ PreT in both age groups striatum.


Tert-buthylhydroquinone pre-conditioning exerts dual effects in old female rats exposed to 3-nitropropionic acid
Nrf2 nuclear and cytosolic levels. A. Representative images of Nrf2 nuclear accumulation (Nuc Frac) in adult and old animals after tBHQ PreT and densitometric analysis. For Adult, ap<0.05,bp<0.01 vs Ct, cp<0.001 vs 3-NP. For Old, ap<0.01 vs Ct, bp<0.05 vs 3-NP. B. Representative images of Nrf2 content in the cytosolic fraction (Cyt Frac) in adult and old animals and densitometric analysis. ap<0.01 vs Ct, bp<0.05 vs 3NP. C. Representative images of antioxidant enzymes regulated by Nrf2 evaluated in the Cyt Frac in adult and old animals and densitometric analysis. ap<0.001, bp<0.05 vs Ct, cp<0.001,dp<0.05 vs 3-NP. Similar results were obtained from three independent experiments. All data are represented as mean±SD (n=3 in each group).
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5384325&req=5

f0030: Nrf2 nuclear and cytosolic levels. A. Representative images of Nrf2 nuclear accumulation (Nuc Frac) in adult and old animals after tBHQ PreT and densitometric analysis. For Adult, ap<0.05,bp<0.01 vs Ct, cp<0.001 vs 3-NP. For Old, ap<0.01 vs Ct, bp<0.05 vs 3-NP. B. Representative images of Nrf2 content in the cytosolic fraction (Cyt Frac) in adult and old animals and densitometric analysis. ap<0.01 vs Ct, bp<0.05 vs 3NP. C. Representative images of antioxidant enzymes regulated by Nrf2 evaluated in the Cyt Frac in adult and old animals and densitometric analysis. ap<0.001, bp<0.05 vs Ct, cp<0.001,dp<0.05 vs 3-NP. Similar results were obtained from three independent experiments. All data are represented as mean±SD (n=3 in each group).
Mentions: Nrf2 distribution in nuclear and cytosolic fractions was evaluated in the brains from old and adult treated animals. Differential effects in both age groups were observed (Fig. 6A). The old animals slightly increased Nrf2 nuclear translocation with tBHQ while in increased Nrf2 was found in the nuclear fraction of adult animals treated with 3-NP alone, (p<0.01) when compared to the control, tBHQ and PreT treated animals. In contrast, nuclear Nrf2 accumulation in old animals was only observed (10%, p<0.01) in tBHQ treated rats. Both animal groups, adult and old, decreased Nrf2 nuclear accumulation after tBHQ PreT (Fig. 6A). On the contrary, tBHQ PreT induced a greater cytoplasmic Nrf2 accumulation in adult animals (60%, p<0.01), while in old animals Nrf2 levels decreased (p<0.05) compared to the 3-NP group, which did not modify the Nrf2 cytosolic content (Fig. 6B). Our data indicate that Nrf2 is not efficiently translocated to the nucleus after tBHQ PreT in both age groups striatum.

View Article: PubMed Central - PubMed

ABSTRACT

The brain is a very susceptible organ to structural and functional alterations caused by oxidative stress and its vulnerability increases with age. Understanding the antioxidant response activated by the transcription factor Nrf2 has become very important in the aging field in order to activate cellular protection. However, the role of Nrf2 inducers during old age has not been completely understood. Our aim was to activate the Nrf2 pathway by pre-treating old rats with a widely used Nrf2-inducer, tert-buthylhydroquinone (tBHQ), prior to 3-nitropropionic acid (3-NP) insult, in order to evaluate its effects at a behavioral, morphological and biochemical levels. 3-NP has been used to reproduce the biochemical and pathophysiological characteristics of Huntington's disease due to an oxidative effect. Our results suggest that tBHQ confers an important protective effect against 3-NP toxicity; nevertheless, Nrf2 seems not to be the main protective pathway associated to neuroprotection. Hormetic responses include the activation of more than one transcription factor. Nrf2 and NF&kappa;B are known to simultaneously initiate different cellular responses against stress by triggering parallel mechanisms, therefore NF&kappa;B nuclear accumulation was also evaluated.

No MeSH data available.