Long-term melatonin treatment delays ovarian aging.

Ovarian aging is characterized by gradual declines in oocyte quantity and quality. Melatonin is considered an anti-aging agent due to its cytoprotective actions as an antioxidant. This study examined whether long-term melatonin treatment would delay ovarian aging in mice. Female ICR mice (10 weeks old) were given melatonin-containing water (100 µg/mL; melatonin) or water only until 43 weeks of age. Their oocytes were recovered from the oviduct, and in vitro fertilization was performed. The ovaries were used for a histological analysis of the number of follicles. The mRNA expression of the aging-related sirtuin genes (SIRT1, SIRT3) and the autophagy-related gene (LC3) and the telomere length of the ovarian chromosomes were analyzed. Transcriptome changes in the ovaries were also characterized using microarray. The number of ovulated oocytes decreased with age; however, it was greater in melatonin-treated mice than that from control animals. The decreased fertilization rate and blastocyst rate during aging also were higher in the melatonin-treated mice than in the controls, as were the numbers of primordial, primary, and antral follicles. The mRNA expression of SIRT1 and LC3 and telomere length were enhanced due to melatonin treatment. Seventy-eight genes that were downregulated during aging and upregulated by melatonin were identified by a microarray analysis. Forty of these 78 genes were ribosome-related genes, and a free radical scavenging network was identified. The present results indicate that melatonin delays ovarian aging by multiple mechanisms including antioxidant action, maintaining telomeres, stimulating SIRT expression and ribosome function, and by reducing autophagy.

Effects of phytoncides on blood pressure under restraint stress in SHRSP.

1. Phytoncides are volatile substances released mainly from trees. We studied whether phytoncides can reduce stress responses in stroke-prone spontaneously hypertensive rats (SHRSP). 2. Under the restraint stress, SHRSP exposed to phytoncides showed lower blood pressure than those without the exposure (186.8 +/- 3.9 vs 207.7 +/- 3.4 mmHg, respectively, P < 0.01 by Student's t-test). 3. Consistent with the observation above, the plasma concentration of catecholamines under the restraint stress was lower in the phytoncides group than in the control group. 4. Based on these results, we concluded that phytoncides reduced the cardiovascular response to restraint stress in SHRSP.

Adrenocorticotropic tumor cells transplanted into mouse embryos affect pancreatic histogenesis.

A wide range of individual differences exist in the total number of functional and structural units in each organ, such as ß cells in pancreatic islands, and these units are the basis of the organ's overall function, including its functional reserve. The endocrine environment may influence organ histogenesis, during which functional and structural units are formed and increase in number. We analyzed the effects of a continuous high level of adrenocorticotropic hormone (ACTH) and/or secondarily induced glucocorticoid on histogenesis of the pancreas in mouse embryos. Pituitary tumor-derived AtT20 cells, which secrete ACTH continuously, were injected subcutaneously into mouse embryos at embryonic day (E) 12.5, and the embryos were allowed to develop exo utero until E18.5 (AtT20 group). E18.5 AtT20 group embryos with high ACTH levels (23.74 ± 6.19 ng/mL vs control group, 0.48 ± 0.40 ng/mL, P < 0.05) were examined for the effects on histogenesis of the pancreas. Using serial sections of the E18.5 pancreas, we stereologically measured the volumes, and counted total cell numbers and numbers of mitotic or pyknotic cells of the whole pancreas, endocrine and exocrine cells, and glucagon-immunopositive α cells and insulin-immunopositive ß cells in the endocrine part. Although the volumes of the whole pancreas and exocrine part did not change significantly, in the AtT20 group the endocrine part was significantly larger, with fewer pyknotic cells and lower ratios of α and ß cells than in the control group. These results suggest that the high level of ACTH and/or glucocorticoid affects histogenesis of the pancreas.

Leptin and its intracellular signaling pathway maintains the neurosphere.

Leptin is associated with the maintenance of epidermal growth factor (EGF)-reactive neural lineage cells, including the neural progenitors. One-day treatment with leptin (10, 100, or 1000 ng/ml) followed by EGF treatment increased the number of small-sized and mid-sized colonies compared with the nonleptin treatment. Leptin prevented the inactivation of the phosphatidylinositol 3-kinase (PI3 K) and extracellular signal regulated kinase (ERK) pathways in neurosphere cells cultured in the non-EGF medium. Bromodeoxyuridine (BrdU) incorporation into the neurosphere cells induced by leptin was suppressed by LY294002, a PI3 K inhibitor, but not by U0126, a MEK1/2 inhibitor, which activates ERK1/2, although U0126 decreased phosphorylated extracellular signal regulated kinase levels. These results suggest that leptin maintains the self-renewal ability and EGF reactivity of immature neural lineage cells and the signal is mediated, at least in part, by the PI3 K pathway.

Biotransformation of bromosesquiterpenes by marine fungi.

Biotransformation of bromosesquiterpenes was investigated with two types of fungi, Rhinocladiella atrovirens NRBC 32362 and also Rhinocladiella sp. K-001, isolated from the Okinawan brown alga Stypopodium zonale. R. atrovirens NRBC 32362 converted aplysistatin 1 into three compounds 5alpha-hydroxyaplysistatin 4, 5alpha-hydroxyisoaplysistatin 5 and 9beta-hydroxyaplysistatin 6. Transformation of 1, palisadin A 2 and 12-hydroxypalisadin B 3 by Rhinocladiella sp. K-001 gave two compounds, 3,4-dihydroaplysistatin 7 and 9,10-dehydrobromopalisadin A 8.

Biotransformation of (+/-)-2-methylcyclohexanone by fungi.

The biotransformation of 2-methylcyclohexanone (1) using 16 fungal strains and some mushroom cultures was investigated. Fusarium sp. was one of the effective biocatalysts for oxidoreduction of 2-methylcyclohexanone (1). cis-2-Methylcyclohexanol (2a) was isomerized to trans-2-methylcyclohexanol (2b) by Fusarium sp. In addition, the corresponding lactones 3 was obtained by Baeyer-Villiger oxidation using Fusarium sp. AP-2 (46%, 94% ee).