Distribution of Transmissible Amyloid Proteins in the Liver with Apolipoprotein A-II Amyloidosis

Article信州医学雑誌 64(4): 183-194(2016)journal articl

Amyloid fibrils formed by selective N-, C-terminal sequences of mouse apolipoprotein A-II

In mice, amyloidogenic type C apolipoprotein A-II (apoA-II) forms amyloid fibrils in age-associated amyloidosis. To understand the mechanism of amyloid fibril formation by apoA-II, we examined the polymerization of synthetic partial peptides of apoA-II in vitro. None of the partial apoA-II peptides polymerized into amyloid fibrils when tested as a single species mixture. We found a unique mechanism in which N- and C-terminal peptides associated into amyloid fibrils in a 1:1 ratio at pH 2.5. The 11-residue amino acid sequence (6-16), which is a common sequence of type B apoA-II and type C apoA-II proteins in amyloidosis-resistant mice and amyloidosis-susceptible mice, respectively, was critical for polymerization into amyloid fibrils. The 18-residue-long amino acid sequence (48-65) is also necessary for nucleation, but not for the extension phase. These findings suggest that there may be different mechanisms underlying the nucleation and extension phases of apoA-II amyloid fibril formation. We also found that amino acid substitutions between type B apoA-II (Pro5, Val38) and type C apoA-II (Gln5, Ala38) did not affect either phase. The strategy of using synthetic partial peptides of amyloidogenic proteins in vitro is a useful system for understanding amyloid fibril formation and for the development of novel therapies.ArticleBIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS. 1794(10):1517-1529 (2009)journal articl

Effects of mild calorie restriction and high-intensity interval walking in middle-aged and older overweight Japanese

We investigated whether a combination of mild calorie restriction (MCR) and high-intensity interval walking (HIW) improved physical fitness more than HIW alone in middle-aged and older overweight Japanese (40-69 years old, BMI >= 23.6 kg/m(2)). Forty-seven women and 16 men were divided into MCR + HIW and HIW groups. All subjects performed HIW: >= 5 sets of 3-min low-intensity walking (40% peak aerobic capacity for walking, VO2peak) and 3-min high-intensity walking (>= 70% VO2peak) per day, >= 4 days per week, for 16 weeks while energy expenditure was monitored with a tri-axial accelerometer. The MCR + HIW group consumed meal replacement formula (240 kcal): a mixture of low-carbohydrates and -fat and high-protein, for either lunch or dinner everyday and therefore, had similar to 87% of the energy intake of the HIW group during the intervention period. Although the HIW group showed improvements in BMI, blood pressure, and several blood chemicals, the MCR + HIW group had greater improvement. Moreover, the medical expenditure for the 6 months including the intervention period was 59% lower in the MCR + HIW group than in the HIW group. Our strategy of a short-term combination of MCR and HIW may thus prevent lifestyle-associated diseases and improve health in middle-aged and older overweight Japanese.ArticleEXPERIMENTAL GERONTOLOGY. 44(10):666-675 (2009)journal articl

Coenzyme Q10 Prevents Senescence and Dysfunction Caused by Oxidative Stress in Vascular Endothelial Cells

ArticleOxidative medicine and cellular longevity 2018 : 3181759, (2018)journal articl

Glavonoid-rich oil supplementation reduces stearoyl-coenzyme A desaturase 1 expression and improves systemic metabolism in diabetic, obese KK-Ay mice

Aims: Glavonoid-rich oil (GRO) derived from ethanol extraction of licorice (Glycyrrhiza glabra Linne) root has been reported to have beneficial effects on health. In this study, we aimed to determine the effect of long-term administration of GRO on metabolic disorders and to elucidate the molecular mechanism. Main methods: Female obese, type 2 diabetic KK-Ay mice were fed diets supplemented with 0.3% or 0.8% GRO (w/w) for 4–12 weeks. Mice were euthanized and autopsied at 20 weeks old. The effects of GRO on lipid and glucose metabolism were evaluated by measuring physiological and biochemical markers using mRNA sequencing, quantitative reverse-transcription PCR, and western blot analyses. Key findings: Compared to mice fed the control diet, GRO-supplemented mice had reduced body and white adipose tissue weights, serum levels of triglycerides and cholesterol, and improved glucose tolerance, while food intake was not affected. We found remarkable reductions in the gene expression levels of stearoyl-coenzyme A desaturase 1 (Scd1) and pyruvate dehydrogenase kinase isoenzyme 4 (Pdk4) in the liver, in addition to decreased expression of fatty acid synthase (Fasn) in inguinal white adipose tissue (iWAT). These results suggest that GRO supplementation improves lipid profiles via reduced de novo lipogenesis in the liver and white adipose tissue. Glucose metabolism may also be improved by increased glycolysis in the liver. Significance: Our analysis of long-term supplementation of GRO in obese and diabetic mice should provide novel insight into preventing insulin resistance and metabolic syndromes

Glavonoid-rich oil supplementation reduces stearoyl-coenzyme A desaturase 1 expression and improves systemic metabolism in diabetic, obese KK-Ay mice

ArticleBiomedicine & pharmacotherapy 140 : 111714, (2021)journal articl

Coenzyme Q10 Prevents Senescence and Dysfunction Caused by Oxidative Stress in Vascular Endothelial Cells

Oxidative damage in endothelial cells is proposed to play an important role in endothelial dysfunction and atherogenesis. We previously reported that the reduced form of coenzyme Q10 (CoQ10H2) effectively inhibits oxidative stress and decelerates senescence in senescence-accelerated mice. Here, we treated human umbilical vein endothelial cells (HUVECs) with H2O2 and investigated the protective effect of CoQ10H2 against senescence, oxidative damage, and reduction in cellular functions. We found that CoQ10H2 markedly reduced the number of senescence-associated β-galactosidase-positive cells and suppressed the expression of senescence-associated secretory phenotype-associated genes in H2O2-treated HUVECs. Furthermore, CoQ10H2 suppressed the generation of intracellular reactive oxygen species (ROS) but promoted NO production that was accompanied by increased eNOS expression. CoQ10H2 prevented apoptosis and reductions in mitochondrial function and reduced migration and tube formation activity of H2O2-treated cells. The present study indicated that CoQ10H2 protects endothelial cells against senescence by promoting mitochondrial function and thus could delay vascular aging