Carnosine content in skeletal muscle is dependent on vitamin B6 status in rats

Carnosine, a histidine-containing dipeptide, is well known to be associated with skeletal muscle performance. However, there is limited information on the effect of dietary micronutrients on muscle carnosine level. Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, is involved in amino acid metabolisms in the body as a cofactor. We hypothesized that enzymes involved in β-alanine biosynthesis, the rate-limiting precursor of carnosine, may also be PLP dependent. Thus, we examined the effects of dietary vitamin B6 on the muscle carnosine content of rats. Male and female rats were fed a diet containing 1, 7, or 35 mg pyridoxine (PN) HCl/kg for 6 weeks. Carnosine in skeletal muscles was quantified by ultra-performance liquid chromatography coupled with tandem mass spectrometry. In the gastrocnemius muscle of male rats, carnosine concentration was significantly higher in the 7 and 35 mg groups (+70 and +61%, respectively) than in the 1 mg PN HCl/kg group, whereas that in the soleus muscle of male rats was significantly higher only in the 7 mg group (+43%) than in the 1 mg PN HCl/kg group (P < 0.05). In both muscles of female rats, carnosine concentration was significantly higher in the 7 and 35 mg groups (+32 to +226%) than in the 1 mg PN HCl/kg group (P < 0.05). We also found that, compared to the 1 mg group, β-alanine concentrations in the 7 and 35 mg groups were markedly elevated in gastrocnemius muscles of male (+153 and +148%, respectively, P < 0.05) and female (+381 and +437%, respectively, P < 0.05) rats. Noteworthy, the concentrations of ornithine in the 7 and 35 mg groups were decreased in gastrocnemius muscles of male rats (-46 and -54%, respectively, P < 0.05), which strongly inversely correlated with β-alanine concentration (r = -0.84, P < 0.01). In humans, 19% lower muscle carnosine content was found in soleus muscle of women of the lower plasma PLP tertile, but this was not observed in gastrocnemius muscle or in men. We conclude that adequate dietary vitamin B6 is essential for maintaining carnosine in skeletal muscles of rats. Significantly lower soleus carnosine content among women close to PLP deficiency suggests that a similar phenomenon exists in the humans

Alisol B, a triterpene from Alismatis rhizoma (dried rhizome of Alisma orientale), inhibits melanin production in murine B16 melanoma cells

To develop new whitening agents from natural products, we screened 80 compounds derived from crude drugs in Kampo medicine in a melanin synthesis inhibition assay using murine B16 melanoma cells. The screen revealed that treatment with alisol B, a triterpene from Alismatis rhizoma, significantly decreased both melanin content and cellular tyrosinase activity in B16 cells. However, alisol B did not directly inhibit mushroom tyrosinase activity in vitro. Therefore, we investigated the mechanism underlying the inhibitory effect of alisol B on melanogenesis. Alisol B suppressed mRNA induction of tyrosinase and its transcription factor, microphthalmia-associated transcription factor (MITF). Furthermore, alisol B reduced the phosphorylation of CREB and maintained the activation of ERK1/2. These results suggest that the reduction in melanin production by alisol B is due to the downregulation of MITF through the suppression of CREB and activation of ERK, and that alisol B may be useful as a new whitening agent

Pengaruh Dimensi Benda Uji Terhadap Kuat Tekan Beton

Kuat tekan adalah karakteristik mekanik utama dari beton yang dapat diketahui melalui penelitian uji tekan di laboratorium terhadap benda uji. Baik dalam bentuk kubus ataupun silinder dengan ukuran standar: 10cm x 10cm x 10cm dan 15cm x 15cm untuk kubus dan 10cm x 20cm dan 15cm x 30cm untuk silinder. Untuk mendapatkan informasi mengenai kecendrungan harga kuat tekan beton dengan variasi dimensi benda uji, telah dilakukan penelitian-penelitian di laboratoriun untuk mendapatkan komposisi campuran tertentu pada umur beton 28 hari, variasi ukuran benda uji dibuat: 10cm x 10cm x 10cm, 12,5cm x 12,5cm x 12,5cm dan 15cm x 15cm x 15cm untuk kubus dan 10cm x 20cm, 12,5cm x 25cm dan 15cm x 30cm untuk silinder. Dengan jumlah benda uji masing-masing 20 buah untuk setiap ukuran benda uji. Melalui prosedur standar pengujian kuat tekan dan menggunakan formula-formula baku perhitungan tekan rata-rata diperoleh informasi bahwa peningkatan ukuran dimensi benda uji menghasilkan penurunan kuat tekan rata-rata, untuk benda uji kubus dengan ukuran masing-masing: 10cm x 10cm x 10cm, 12,5cm x 12,5cm x 12,5cm dan 15cm x 15cm x 15cm diperoleh kuat tekan rata-rata masing-masing: 32,86MPa, 31,26MPa dan 31,036MPa. Sedangkan untuk silinder dengan kururan 10cm x 20cm, 12,5cm x 25cm dan 15cm x 30cm diperoleh kuat tekan rata-rata masing-masing: 31,47MPa, 30,85MPa dan 30,44MPa

The serum amyloid A3 promoter-driven luciferase reporter mice is a valuable tool to image early renal fibrosis development and shows the therapeutic effect of glucosyl-hesperidin treatment

Tubulointerstitial fibrosis is a progressive process affecting the kidneys, causing renal failure that can be life-threatening. Thus, renal fibrosis has become a serious concern in the ageing population; however, fibrotic development cannot be diagnosed early and assessed noninvasively in both patients and experimental animal models. Here, we found that serum amyloid A3 (Saa3) expression is a potent indicator of early renal fibrosis; we also established in vivo Saa3/C/EBPβ-promoter bioluminescence imaging as a sensitive and specific tool for early detection and visualization of tubulointerstitial fibrosis. Saa3 promoter activity is specifically upregulated in parallel with tumor necrosis factor α (TNF-α) and fibrotic marker collagen I in injured kidneys. C/EBPβ, upregulated in injured kidneys and expressed in tubular epithelial cells, is essential for the increased Saa3 promoter activity in response to TNF-α, suggesting that C/EBPβ plays a crucial role in renal fibrosis development. Our model successfully enabled visualization of the suppressive effects of a citrus flavonoid derivative, glucosyl-hesperidin, on inflammation and fibrosis in kidney disease, indicating that this model could be widely used in exploring therapeutic agents for fibrotic diseases.This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to No. Y)

ナトリウム利尿ペプチドC型受容体の発現制御に関する研究

京都大学0048新制・論文博士博士(農学)乙第10220号論農博第2259号新制||農||789(附属図書館)学位論文||H11||N3324(農学部図書室)UT51-99-S337(主査)教授 清水 昌, 教授 吉川 正明, 教授 伏木 亨学位規則第4条第2項該当Doctor of Agricultural ScienceKyoto UniversityDA

The effects of eccentric contraction on myofibrillar proteins in rat skeletal muscle

The present study investigated the effects of eccentric muscle contractions (ECC) on the content of myofibrillar proteins (my-proteins) and the catalytic activity of myofibrillar ATPase (my-ATPase) in skeletal muscles. Rat extensor digitorum longus and tibialis anterior muscles were exposed to 200-repeated ECC or isometric contractions (ISC) and used for measures of force output and for biochemical analyses, respectively. Whereas in ISC-treated muscles, full restoration of tetanic force was attained after 2 days of recovery, force developed by ECC-treated muscles remained depressed (P<0.05) after 6 days. The total my-protein content and the relative content of myosin heavy chain (MHC) in total my-proteins were unaltered during 4 days of recovery after ECC, but fell (P<0.05) to 55.9 and 63.4% after 6 days of recovery, respectively. my-ATPase activity expressed on a my-protein weight basis was unaltered immediately after ECC. However, it decreased (P<0.05) to 75.3, 45.3, and 49.3% after 2, 4 and 6 days of recovery, respectively. Total maximal calpain activity measured at 5 mM Ca2+ was significantly augmented (P<0.05) after 2 days of recovery, reaching a level of threefold higher after 6 days. These alterations were specific for ECC and not observed for ISC. These results suggest that depressions in my-ATPase activity contribute to ECC-induced decreases in force and power which can take a number of days to recover

Identification and physiological evaluation of the components from Citrus fruits as potential drugs for anti-corpulence and anticancer

On the basis of monitoring the prevention of accumulation of lipid droplets in mouse 3T3-L1 preadipocyte cells and inhibition of the proliferation of human colon cancer HT-29 cells, effective anti-corpulence and anticancer compounds were isolated from the peel of Citrus fruits. These bioactive components were identified as polymethoxyflavones and coumarin derivatives by spectroscopic analyses. 5-Hydroxy-6,7,8,3′,4′-pentamethoxyflavone had the greatest anti-corpulence effects and 3,5,6,7,8,3′,5′-heptamethoxyflavone had the greatest anticancer effects. Furthermore, distributions of those bioactive components in the peel of 10 species of Citrus fruits were demonstrated by HPLC analyses