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Dietary Tocotrienol/γ-Cyclodextrin Complex Increases Mitochondrial Membrane Potential and ATP Concentrations in the Brains of Aged Mice.

Schloesser A, Esatbeyoglu T, Piegholdt S, Dose J, Ikuta N, Okamoto H, Ishida Y, Terao K, Matsugo S, Rimbach G - Oxid Med Cell Longev (2015)

Bottom Line: However, little is known about the effect of dietary T3 on mitochondrial function in vivo.In this study, we monitored the effect of a dietary T3/γ-cyclodextrin complex (T3CD) on mitochondrial membrane potential and ATP levels in the brain of 21-month-old mice.Dietary T3CD significantly increased mitochondrial membrane potential and ATP levels compared to those of controls.

View Article: PubMed Central - PubMed

Affiliation: Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Straße 6, 24118 Kiel, Germany.

ABSTRACT
Brain aging is accompanied by a decrease in mitochondrial function. In vitro studies suggest that tocotrienols, including γ- and δ-tocotrienol (T3), may exhibit neuroprotective properties. However, little is known about the effect of dietary T3 on mitochondrial function in vivo. In this study, we monitored the effect of a dietary T3/γ-cyclodextrin complex (T3CD) on mitochondrial membrane potential and ATP levels in the brain of 21-month-old mice. Mice were fed either a control diet or a diet enriched with T3CD providing 100 mg T3 per kg diet for 6 months. Dietary T3CD significantly increased mitochondrial membrane potential and ATP levels compared to those of controls. The increase in MMP and ATP due to dietary T3CD was accompanied by an increase in the protein levels of the mitochondrial transcription factor A (TFAM). Furthermore, dietary T3CD slightly increased the mRNA levels of superoxide dismutase, γ-glutamyl cysteinyl synthetase, and heme oxygenase 1 in the brain. Overall, the present data suggest that T3CD increases TFAM, mitochondrial membrane potential, and ATP synthesis in the brains of aged mice.

No MeSH data available.


Effect of tocotrienol/γ-cyclodextrin supplementation on the mRNA levels of Sod2, Hmox1, Gclm, Gpx4, and Cat, proteasomal activity, and the BACE1 protein levels in mouse brain. Relative mRNA levels of (a) Sod2, (b) Hmox1, (c) Gclm, (d) Gpx4, and (e) Cat were determined by qRT-PCR and were related to the mean of the housekeeping gene expression. (f) Proteasomal activity was measured in the brain tissue by releasing the initially quenched fluorescence signal of the substrate through cleavage by the specific proteasome site. (g) BACE1 protein levels were determined by Western blotting and subsequent densitometric analysis of target bands. Target protein expression was related to the total protein fluorescence transferred to the PVDF membrane. Representative blots from one of 5–8 animals per group are shown. Values are the means + SEM from 5 to 8 animals per group.
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fig3: Effect of tocotrienol/γ-cyclodextrin supplementation on the mRNA levels of Sod2, Hmox1, Gclm, Gpx4, and Cat, proteasomal activity, and the BACE1 protein levels in mouse brain. Relative mRNA levels of (a) Sod2, (b) Hmox1, (c) Gclm, (d) Gpx4, and (e) Cat were determined by qRT-PCR and were related to the mean of the housekeeping gene expression. (f) Proteasomal activity was measured in the brain tissue by releasing the initially quenched fluorescence signal of the substrate through cleavage by the specific proteasome site. (g) BACE1 protein levels were determined by Western blotting and subsequent densitometric analysis of target bands. Target protein expression was related to the total protein fluorescence transferred to the PVDF membrane. Representative blots from one of 5–8 animals per group are shown. Values are the means + SEM from 5 to 8 animals per group.

Mentions: Dietary T3CD slightly increased (44% increase) Sod2 (Figure 3(a)) compared to that of controls. We also observed slightly higher Hmox1 (22% increase) and Gclm (14% increase) levels as well as higher proteasomal activity (28% increase) in the brains of mice fed the T3CD enriched diet; however, the differences did not reach statistical significance (Figures 3(b), 3(c), and 3(f)). Brain Gpx4 and Cat mRNA concentrations (Figures 3(d) and 3(e)) remained unchanged by the different dietary treatments.


Dietary Tocotrienol/γ-Cyclodextrin Complex Increases Mitochondrial Membrane Potential and ATP Concentrations in the Brains of Aged Mice.

Schloesser A, Esatbeyoglu T, Piegholdt S, Dose J, Ikuta N, Okamoto H, Ishida Y, Terao K, Matsugo S, Rimbach G - Oxid Med Cell Longev (2015)

Effect of tocotrienol/γ-cyclodextrin supplementation on the mRNA levels of Sod2, Hmox1, Gclm, Gpx4, and Cat, proteasomal activity, and the BACE1 protein levels in mouse brain. Relative mRNA levels of (a) Sod2, (b) Hmox1, (c) Gclm, (d) Gpx4, and (e) Cat were determined by qRT-PCR and were related to the mean of the housekeeping gene expression. (f) Proteasomal activity was measured in the brain tissue by releasing the initially quenched fluorescence signal of the substrate through cleavage by the specific proteasome site. (g) BACE1 protein levels were determined by Western blotting and subsequent densitometric analysis of target bands. Target protein expression was related to the total protein fluorescence transferred to the PVDF membrane. Representative blots from one of 5–8 animals per group are shown. Values are the means + SEM from 5 to 8 animals per group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig3: Effect of tocotrienol/γ-cyclodextrin supplementation on the mRNA levels of Sod2, Hmox1, Gclm, Gpx4, and Cat, proteasomal activity, and the BACE1 protein levels in mouse brain. Relative mRNA levels of (a) Sod2, (b) Hmox1, (c) Gclm, (d) Gpx4, and (e) Cat were determined by qRT-PCR and were related to the mean of the housekeeping gene expression. (f) Proteasomal activity was measured in the brain tissue by releasing the initially quenched fluorescence signal of the substrate through cleavage by the specific proteasome site. (g) BACE1 protein levels were determined by Western blotting and subsequent densitometric analysis of target bands. Target protein expression was related to the total protein fluorescence transferred to the PVDF membrane. Representative blots from one of 5–8 animals per group are shown. Values are the means + SEM from 5 to 8 animals per group.
Mentions: Dietary T3CD slightly increased (44% increase) Sod2 (Figure 3(a)) compared to that of controls. We also observed slightly higher Hmox1 (22% increase) and Gclm (14% increase) levels as well as higher proteasomal activity (28% increase) in the brains of mice fed the T3CD enriched diet; however, the differences did not reach statistical significance (Figures 3(b), 3(c), and 3(f)). Brain Gpx4 and Cat mRNA concentrations (Figures 3(d) and 3(e)) remained unchanged by the different dietary treatments.

Bottom Line: However, little is known about the effect of dietary T3 on mitochondrial function in vivo.In this study, we monitored the effect of a dietary T3/γ-cyclodextrin complex (T3CD) on mitochondrial membrane potential and ATP levels in the brain of 21-month-old mice.Dietary T3CD significantly increased mitochondrial membrane potential and ATP levels compared to those of controls.

View Article: PubMed Central - PubMed

Affiliation: Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Straße 6, 24118 Kiel, Germany.

ABSTRACT
Brain aging is accompanied by a decrease in mitochondrial function. In vitro studies suggest that tocotrienols, including γ- and δ-tocotrienol (T3), may exhibit neuroprotective properties. However, little is known about the effect of dietary T3 on mitochondrial function in vivo. In this study, we monitored the effect of a dietary T3/γ-cyclodextrin complex (T3CD) on mitochondrial membrane potential and ATP levels in the brain of 21-month-old mice. Mice were fed either a control diet or a diet enriched with T3CD providing 100 mg T3 per kg diet for 6 months. Dietary T3CD significantly increased mitochondrial membrane potential and ATP levels compared to those of controls. The increase in MMP and ATP due to dietary T3CD was accompanied by an increase in the protein levels of the mitochondrial transcription factor A (TFAM). Furthermore, dietary T3CD slightly increased the mRNA levels of superoxide dismutase, γ-glutamyl cysteinyl synthetase, and heme oxygenase 1 in the brain. Overall, the present data suggest that T3CD increases TFAM, mitochondrial membrane potential, and ATP synthesis in the brains of aged mice.

No MeSH data available.