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Calorie restriction increases telomerase activity, enhances autophagy, and improves diastolic dysfunction in diabetic rat hearts.

Makino N, Oyama J, Maeda T, Koyanagi M, Higuchi Y, Tsuchida K - Mol. Cell. Biochem. (2015)

Bottom Line: Echocardiography showed that OLETF-CR improved the left ventricular diastolic dysfunction without changes in the left ventricular dimension.This study revealed that CR increases cardiac telomerase activity without TL attrition, and significantly ameliorates diastolic dysfunction.These findings suggest that cardiac telomerase activity may play an important role in the maintenance of normal cardiac function.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular and Clinical Gerontology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu, 874-0838, Japan, makino0108@gmail.com.

ABSTRACT
The aims of this study were to investigate the impact of caloric restriction (CR) on cardiac telomere biology in an animal model of diabetes and to examine the signal transduction involved in cell senescence as well as cardiac function. Male 8-week-old Otsuka Long-Evans Tokushima fatty (OLETF) diabetic rats were divided into two groups: a group fed ad libitum (OLETF-AL) and a group fed with CR (OLETF-CR: 30% energy reduction). Long-Evans Tokushima Otsuka (LETO) non-diabetic rats were used as controls. LETO rats were also divided into two groups: a CR (LETO-CR) group and a group fed AL (LETO-AL). At 40 weeks of age, the body weight was decreased by 9.7% and the insulin resistance was less in OLETF-CR rats. Telomerase activity in OLETF-CR rats was significantly increased, and telomerase reverse transcriptase was more highly expressed in those rats. However, the telomere length (TL) was not different between AL- and CR-treated rats of each strain. The protein expressions for FoxO1 and FoxO3 were increased in OLETF-AL rats, but the levels of phosphorylated (p)-Akt were decreased compared to those in OLETF-CR rats. Autophagic LC3II signals revealed significant increases in OLETF-CR rats. Echocardiography showed that OLETF-CR improved the left ventricular diastolic dysfunction without changes in the left ventricular dimension. This study revealed that CR increases cardiac telomerase activity without TL attrition, and significantly ameliorates diastolic dysfunction. These findings suggest that cardiac telomerase activity may play an important role in the maintenance of normal cardiac function.

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Western immunoblotting for light chain 3 (LC3) and beclin1. a Representative Western immunoblots showing the expression of conjugated (LC3-II), cytosolic (LC3-I) LC3, beclin1 and GAPDH. b Densitometric analysis of beclin1 and the LC3-II/LC3-I ratio. Data are the mean ± SE of 5 experiments. ap < 0.05 versus LETO-AL rats; bp < 0.05 versus OLETF-AL rats. c Immunofluorescent study of LC3 protein levels in the heart sections with green signals indicating LC3 deposition. Original magnification, ×630. DAPI staining was performed as counterstaining
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Fig7: Western immunoblotting for light chain 3 (LC3) and beclin1. a Representative Western immunoblots showing the expression of conjugated (LC3-II), cytosolic (LC3-I) LC3, beclin1 and GAPDH. b Densitometric analysis of beclin1 and the LC3-II/LC3-I ratio. Data are the mean ± SE of 5 experiments. ap < 0.05 versus LETO-AL rats; bp < 0.05 versus OLETF-AL rats. c Immunofluorescent study of LC3 protein levels in the heart sections with green signals indicating LC3 deposition. Original magnification, ×630. DAPI staining was performed as counterstaining

Mentions: Our results strongly suggest that CR has the potential to improve diastolic dysfunction in the diabetic myocardium, and that these effects might be attributable to the up-regulation of telomerase activity in addition to ameliorating oxidative DNA damage. To clarify which mechanism is mainly responsible for the intracellular signaling for cell survival, we examined the effects of CR on autophagic flux by assessing the expression of LC3-II both in experimental rats fed an AL diet and those fed a CR diet (Fig. 7a, b). An increase in the ratio of LC3-II to the cytosolic form of LC3 (LC3-I) was observed in OLETF-CR rats compared with OLETF-AL rats, but was not in LETO-CR rats. An immunofluorescent study of the levels of LC3 protein showed that the green signals indicating LC3 deposition were increased in the heart tissue of OLETF-CR rats compared to OLETF-AL rats, although those were not between LETO-AL and LETO-CR (Fig. 7c). The expression levels of beclin 1 were not significantly different among the groups in the present study.Fig. 7


Calorie restriction increases telomerase activity, enhances autophagy, and improves diastolic dysfunction in diabetic rat hearts.

Makino N, Oyama J, Maeda T, Koyanagi M, Higuchi Y, Tsuchida K - Mol. Cell. Biochem. (2015)

Western immunoblotting for light chain 3 (LC3) and beclin1. a Representative Western immunoblots showing the expression of conjugated (LC3-II), cytosolic (LC3-I) LC3, beclin1 and GAPDH. b Densitometric analysis of beclin1 and the LC3-II/LC3-I ratio. Data are the mean ± SE of 5 experiments. ap < 0.05 versus LETO-AL rats; bp < 0.05 versus OLETF-AL rats. c Immunofluorescent study of LC3 protein levels in the heart sections with green signals indicating LC3 deposition. Original magnification, ×630. DAPI staining was performed as counterstaining
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4383823&req=5

Fig7: Western immunoblotting for light chain 3 (LC3) and beclin1. a Representative Western immunoblots showing the expression of conjugated (LC3-II), cytosolic (LC3-I) LC3, beclin1 and GAPDH. b Densitometric analysis of beclin1 and the LC3-II/LC3-I ratio. Data are the mean ± SE of 5 experiments. ap < 0.05 versus LETO-AL rats; bp < 0.05 versus OLETF-AL rats. c Immunofluorescent study of LC3 protein levels in the heart sections with green signals indicating LC3 deposition. Original magnification, ×630. DAPI staining was performed as counterstaining
Mentions: Our results strongly suggest that CR has the potential to improve diastolic dysfunction in the diabetic myocardium, and that these effects might be attributable to the up-regulation of telomerase activity in addition to ameliorating oxidative DNA damage. To clarify which mechanism is mainly responsible for the intracellular signaling for cell survival, we examined the effects of CR on autophagic flux by assessing the expression of LC3-II both in experimental rats fed an AL diet and those fed a CR diet (Fig. 7a, b). An increase in the ratio of LC3-II to the cytosolic form of LC3 (LC3-I) was observed in OLETF-CR rats compared with OLETF-AL rats, but was not in LETO-CR rats. An immunofluorescent study of the levels of LC3 protein showed that the green signals indicating LC3 deposition were increased in the heart tissue of OLETF-CR rats compared to OLETF-AL rats, although those were not between LETO-AL and LETO-CR (Fig. 7c). The expression levels of beclin 1 were not significantly different among the groups in the present study.Fig. 7

Bottom Line: Echocardiography showed that OLETF-CR improved the left ventricular diastolic dysfunction without changes in the left ventricular dimension.This study revealed that CR increases cardiac telomerase activity without TL attrition, and significantly ameliorates diastolic dysfunction.These findings suggest that cardiac telomerase activity may play an important role in the maintenance of normal cardiac function.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular and Clinical Gerontology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu, 874-0838, Japan, makino0108@gmail.com.

ABSTRACT
The aims of this study were to investigate the impact of caloric restriction (CR) on cardiac telomere biology in an animal model of diabetes and to examine the signal transduction involved in cell senescence as well as cardiac function. Male 8-week-old Otsuka Long-Evans Tokushima fatty (OLETF) diabetic rats were divided into two groups: a group fed ad libitum (OLETF-AL) and a group fed with CR (OLETF-CR: 30% energy reduction). Long-Evans Tokushima Otsuka (LETO) non-diabetic rats were used as controls. LETO rats were also divided into two groups: a CR (LETO-CR) group and a group fed AL (LETO-AL). At 40 weeks of age, the body weight was decreased by 9.7% and the insulin resistance was less in OLETF-CR rats. Telomerase activity in OLETF-CR rats was significantly increased, and telomerase reverse transcriptase was more highly expressed in those rats. However, the telomere length (TL) was not different between AL- and CR-treated rats of each strain. The protein expressions for FoxO1 and FoxO3 were increased in OLETF-AL rats, but the levels of phosphorylated (p)-Akt were decreased compared to those in OLETF-CR rats. Autophagic LC3II signals revealed significant increases in OLETF-CR rats. Echocardiography showed that OLETF-CR improved the left ventricular diastolic dysfunction without changes in the left ventricular dimension. This study revealed that CR increases cardiac telomerase activity without TL attrition, and significantly ameliorates diastolic dysfunction. These findings suggest that cardiac telomerase activity may play an important role in the maintenance of normal cardiac function.

Show MeSH
Related in: MedlinePlus