| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
Manganese is an essential trace element. However, when a living matter is exposed to an excess amount of manganese, a homeostasis of physiological functions is significantly affected. At present, how the living matters keep thuemselves from the toxic effects of the metal is not known. In this study, we found that excess manganese was localized in a form of particle in a cytoplasmic organelle. We consider that this particular form of manganese is the way for the cells to avoid toxic effects of the metal from cellular functions and is a new concept of detoxification of manganese.
Male rats (Wistar) were administered 0.25 ml of MnC12 solution (20mg/ml) ip or sc, two times a day for 3 weeks. Under anesthesia, rats were killed and the pancreas was excised. The specimen was quickly frozen in a fast drying apparatus and examined by electron microscope connected with Xray-micro activation analyzer. Similar specimens were fractionated by ultracetrifugation to obtain nuclei-rich, mitochondria-ric
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h, lysosomes-rich and post-particular fractions. Manganese contens in these fractions were determined by neutron activation analysis with chemical extraction. Further identification of lysosomes-rich fraction was performed by marker-enzyme activities. The liver, kindey and thyroid were also used as a control organ.
Manganese administration to the rat resulted in the large excess accumulation of the metal in the pancreas and the thyroid, however, rather unchanged the metal contents in the liver.
The electron microscopic observation showed that excess manganese was found in a particular form in the cytoplasm of the pancreatic cells. The particle consisted of manganese, phosphorus, calcium, sulfer and other trace elements in the body. The shape and density of the particles were identical to those of the lysosomes. To examine whether or not the lysosomes contain manganese, subcellular fractionation was performed and the fractions were measured for their manganese contents. The results indicated that manganese was, indeed, localized highly in the lysosomes-rich fraction. Thus, it was concluded that manganese was accumulated in the lysosomes in the pancreas. Manganese was also found in the nucleus but was not detected in mitochondrion by Xray microactivation analysis.
It is possible that the excess manganese in a particular form in cells in kept from cellular functions to avoid toxic effects by manganese. Thus, a formation of granular manganese can be a way of excretory and detoxification processes for excess toxic metals in cells. Less
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