Nutritional consideration for changes in dietary habit and health promotion practices in community health care; from the view point of selenium

The Japanese recommended dietary allowances (RDA) for major and some minor nutrients were revised in 1999, and included those for trace elements such as selenium. The requirement of selenium in animals was first recognized in 1957. It has been shown that cellular glutathione peroxidase (GPx) contains selenium but it was subsequently revealed that selenium has diverse biochemical effects, rather than simply functioning in the enzyme. At least twelve different selenoproteins have been identified. The role of selenium has been known as antioxidant, and non-antioxidant mediated through these enzymes. Now, selenium is well recognized as a preventive factor for cancer and cardiovascular diseases. Several dietary studies have shown that the selenium intake in Japan is adequate. One study estimated daily selenium intake to be 104.2 micrograms/day for adults. This value was 2 or 3 times higher than the lower limit of the safe range of dietary selenium (40 micrograms/day for men and 30 micrograms/day for women) estimated by WHO, and also exceeded the newly established RDA of 55-60 micrograms/day for men and 45 micrograms/day for women by the Japanese Public Health Council. However, the established RDA for selenium is tentative because of a lack of information on the 1) chemical forms of selenium in food, 2) differences in absorption rate and bio-availability in the chemical forms, and 3) interactions with other metals and trace elements. There are two potential problems concerning selenium nutrition in Japan. The first problem is that rice, which is the Japanese staple food, contains less than 0.05 microgram/g selenium whereas U.S. rice contains more than 0.3 microgram/g, probably due to differences in soil chemistry. The second problem is that although studies have shown that seafood, fish, shellfish and oysters, contain high levels of selenium (0.4-0.5 microgram/g), these being the main selenium source for Japanese, the bio-availability in fish is low. Thus, it is likely that the selenium status of those Japanese who eat an imbalanced diet is not sufficient or is not optimal even if the intake exceeds the RDA. Further studies are needed so that community health care specialists have available appropriate knowledge on the role of trace nutrients, including selenium, in human nutrition and health, to promote proper nutritional practices in the community.     

Effect of pancreastatin on cerulein-stimulated pancreatic blood flow and exocrine secretion in anaesthetized rats

BACKGROUND: Pancreastatin (PST) is an inhibitor of pancreatic exocrine secretion in vivo but not in vitro, which suggests that the inhibitory effect of PST is indirect, that is, not mediated by a specific receptor on pancreatic acinar cells. In this study, we investigated the effects of PST on pancreatic exocrine secretion and local pancreatic blood flow in anaesthetized rats to elucidate the participation of PST in indirect regulation of pancreatic exocrine function through blood supply. METHODS: Pancreastatin (100, 200 or 500 pmol/kg per h) was administered intravenously under background infusion of cerulein (0.5 microg/kg per h), a cholecystokinin analogue. Pancreatic exocrine secretion was monitored by volume and protein output of the pancreatic juice and local pancreatic blood flow was measured by the hydrogen gas clearance method. RESULTS: Pancreastatin significantly reduced cerulein-induced local pancreatic blood flow in a dose-dependent manner. Pancreatic exocrine secretion was also reduced significantly by PST dose-dependently. Pancreastatin did not change systemic blood pressure.These results suggested that the reduction of pancreatic blood flow is associated with the reduction of pancreatic exocrine secretion. CONCLUSIONS: We conclude that the mechanism of PST-induced inhibition of pancreatic exocrine secretion is, at least, partly mediated by the reduction of local pancreatic blood flow through blockade, caused by the action of cerulein on pancreatic blood flow.     

Effect of food deprivation on opioid receptor binding in the brain of lean and fatty Zucker rats

The effect of food deprivation on opioid receptor binding was studied in 6 brain regions of lean and fatty Zucker rats; using [3H]dynorphin A. There was no significant difference between lean and fatty rats fed ad libitum in binding parameters for any regions studied. Food deprivation increased Bmax and/or Kd for cortex, midbrain and striatum of lean rats, and the former two regions of fatty rats. These results suggest that food deprivation may influence opioid receptor binding in lean and fatty Zucker rats.     

Chronic hypoxia accelerates the progression of atherosclerosis in apolipoprotein E-knockout mice.

The aim of this study was to investigate the effect of chronic hypoxia on the development and progression of atherosclerosis in apolipoprotein E-knockout (apoE-KO) mice. Male and female apoE-KO mice (6 weeks old) and age- and sex-matched wild-type mice were kept under hypoxic conditions (10.0 +/- 0.5% O2) in a gas chamber or in room air for 3 weeks. Aortic atherosclerotic plaque was not observed in wild-type mice under normoxic or hypoxic conditions. In the apoE-KO mice, however, hypoxia induced proliferation of smooth muscle cells and plaque formation in the aorta, which were not observed under normoxic conditions. Although sexual dimorphism of the response to hypoxia was not observed, these hypoxia-induced atherogenic changes were accompanied by a significant increase of plasma low density lipoprotein (LDL) cholesterol and NADPH-dependent vascular superoxide (O2-) production. Furthermore, matrix metalloproteinase (MMP)-9 was activated in the aorta of apoE-KO mice. In conclusion, chronic hypoxia accelerated the development of atherosclerosis in apoE-KO mice, along with increased O2- production and activated MMP-9 in the aorta.     

Inverse relationship of expression between GM3 and globo-series ganglioside in human renal cell carcinoma

Renal cell carcinoma (RCC) is highly metastatic. We previously showed that expression of globo-series ganglioside is associated with the metastatic potential of RCC. However, the mechanism of metastasis remains largely unknown, and there is no effective therapy for metastasis. It was recently shown that induction of differentiation of colon cancer cells by brefeldin A was accompanied by an increase of GM3 with a concomitant decrease of neolacto-series gangliosides. To get a clue to a new method of therapy for RCC, we investigated whether the similar changes occur in RCC cells expressing globo-series ganglioside. Growth suppression and an increase of GM3 simultaneous with a decrease of monosialosyl galactosyl globoside, a member of globo-series gangliosides, were observed in human RCC cell line ACHN following brefeldin A treatment. The resultant change of the ganglioside profile is inversely related to the ganglioside pattern associated with the malignant potential of RCC and almost coincided with that representative of RCC cases showing favorable prognoses. It is suggested that the inverse relationship of expression between GM3 and globo-series ganglioside is reflected on the degree of malignancy of RCC, and may be useful as one of the indicators for exploiting treatment methods of RCC.     

The anti-apoptotic protein L(*) of Theiler's murine encephalomyelitis virus (TMEV) contains a mitochondrial targeting signal

L(*) protein of TMEV is out-of-frame with the viral polyprotein from an alternative initiation codon AUG, 13 nucleotides downstream from the authentic polyprotein AUG. Anti-apoptotic activity of L(*) was demonstrated by both 'loss of function' and 'gain of function' experiments. However, the precise mechanism(s) of anti-apoptotic activity of L(*) remains to be clarified. In this study, L(*) was demonstrated to be localized to mitochondria. It was also shown by the GFP fusion protein that N-terminal sequence of L(*) may contain a mitochondrial targeting signal (MTS). Surprisingly, L(*)((5-70))-GFP and L(*)((41-70))-GFP were localized to mitochondria although L(*)((1-70))-GFP was distributed in the cytosol, suggesting L(*) has an MTS between amino acid (AA) positions 41 and 70, and that L(*)((1-4)) inhibits its mitochondrial targeting. Furthermore, L(*)((1-70))-GFP was localized to the mitochondria by co-expression of L(*)((65-156)), indicating that L(*)((65-156)) suppresses the inhibition of mitochondrial targeting by L(*)((1-4)). These results suggest that the intra- or inter-molecular interaction of L(*) regulates its mitochondrial localization. It is also suggested that L(*) may inhibit the intrinsic apoptosis through the localization to mitochondria.