小椋 康光

Chelation therapy with tetrathiomolybdate (TTM) was applied to Long-Evans rats with a cinnamon coat-color (LEG rats), an animal model for Wilson disease, to remove copper (Cu) accumulated in the liver in a form bound to metallothionein (MT). Changes in molybdenum (Mo) and Cu concentrations and their biological forms in serum of LEC rats determined at different times after a single intraperitoneal injection were compared with those of Wistar (normal) rats. The change in Mo concentration in serum of normal rats was mono-phasic, whereas in LEC rats it was bi-phasic. The phase in normal rats and the first phase in LEC rats appeared to reflect the process of uptake and disappearance of TTM in the livers of Wistar and LEC rats. On the other hand, the second phase in LEC rats paralleled the changes of Cu and appeared to reflect the complex formation (Cu/thiomolybdate complex) between Mo and Cu accumulated in the liver, The complex was specifically bound to albumin as determined by high performance liquid chromatography with inductively coupled plasma-mass spectrometry (HPLC/ICP-MS). The results suggested that the changes in the Mo concentration in serum reflected the amount of Cu in the liver.

Copper(Cu) accumulating in the liver of LEC rats (Long-Evans rats with a cinnamon-like coat color) is bound to metallothionein (MT). Mechanisms for the removal of Cu by tetrathiomolybdate (TTM) were studied by the high performance liquid chromatography/inductively coupled plasma - mass spectrometry (HPLC/ICP-MS) method. MT containing Cu and cadmium (Cd) (Cu,Cd-MT) was reacted with TTM at a molar ratio of TTM/Cu = 0.5. A complex containing Cu, Cd and molybdenum (Mo) was formed and migrated to a position corresponding to an MT dimer on a gel filtration column. This complex designated previously as a dimer of MT through -S-Cu-S- bridge was revised to be a complex formed between MT and TTM through (MT)-S-Cu-S-(TTM) bridge with differing numbers of TTM bound to MT.

Tetrathiomolybdate (TTM) removes copper (Cu) accumulating in a form bound to metallothionein(MT) in the liver of LEC rats (Long-Evans rats with a cinnamon-like coat color). The first step in the removal of Cu from Cu-MT has been shown to form a complex between MT and TTM through (MT)-S-Cu-S-(TTM) bridges (referred to as MT/TTM complex). Additional TTM was demonstrated to remove Cu from MT/TTM complex as the second step to form Cu/TTM complex by liberating MT. The Cu/TTM complex binds specifically to albumin in serum and to high molecular weight proteins in the absence of albumin, and is assumed to be a form of Cu for efflux by the treatment with TTM.

Tetrathiomolybdate (TTM) removes copper (Cu) accumulating in a form bound to metallothionein (MT) in the liver of LEC rats (Long-Evans rats with a cinnamon-like coat color). The first step in the removal of Cu from Cu-MT has been shown to form a complex between MT and TTM through (MT)-S-Cu-S-(TTM) bridges (referred to as MT/TTM complex). Additional TTM was demonstrated to remove Cu from MT/TTM complex as the second step to form Cu/TTM complex by liberating MT. The Cu/TTM complex binds specifically to albumin in serum and to high molecular weight proteins in the absence of albumin, and is assumed to be a form of Cu for efflux by the treatment with TTM.

Copper (Cu) accumulating in the liver of LEC rats (Long-Evans rats with a cinnamon-like coat color) is bound to metallothionein (MT). Mechanisms for the removal of Cu by tetrathiomolybdate (TTM) were studied by the high performance liquid chromatography/inductively coupled plasma-mass spectrometry (HPLC/ICP-MS) method. MT containing Cu and cadmium (Cd) (Cu,Cd- MT) was reacted with TTM at a molar ratio of TTM/Cu = 0.5. A complex containing Cu, Cd and molybdenum (Mo) was formed and migrated to a position corresponding to an MT dimer on a gel filtration column. This complex designated previously as a dimer of MT through -S-Cu-S- bridge was revised to be a complex formed between MT and TTM through (MT)-S-Cu-S-(TTM) bridge with differing numbers of TTM bound to MT.

Simultaneous speciation of selenium and sulfur species in selenized odorless garlic (Allium sativum L. Shiro) and shallot (Allium ascalonicum) by HPLC-inductively coupled plasma - (octopole reaction system) - mass spectrometry and electrospray ionization 窶・tandem mass spectrometry.