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Title: Hepatic and renal copper-binding proteins and the identification of proteins affected in the brindled mouse model of Menkes disease

Miscellaneous ·
OSTI ID:7061604

The objective of this thesis were to identify proteins involved in the cellular metabolism of copper, and to identify proteins affected in the brindled mouse model of Menkes disease, and inborn of copper metabolism. Initially, hepatocytes were incubated with {sup 64}Cu(II) and cytosolic {sup 64}Cu-binding proteins were resolved on Sephadex G150 columns. The focus was on cytosolic proteins because this fractions reaches a steady-state before the nuclear and mitochondrial fractions, implying the cytosolic proteins deliver copper to other cell compartments. Four {sup 64}Cu-binding fractions were detected at the earliest times and lowest copper concentrations examined; the void volume fraction, a metallothionein(MT) fraction, and fractions peaking at {approx}88kD(I) and {approx}38kD(II), apparent. Superoxide dismutase eluted after the {approx}38kD {sup 64}Cu-binding fraction. The distributions of {sup 64}Cu and {sup 65}Zn were clearly different. The effects of Cu-status on Cu-binding revealed an inverse relationship between Cu-binding to MT and Cu-binding to proteins in fractions I and II. When MT-levels were low in the cytosols from normal mouse and copper-deficient rat hepatocytes, more Cu-binding was detected in fractions I and II; when MT-levels were high as in neonatal rat hepatocytes and brindled mice kidneys, less Cu-binding was detected in these fractions.

Research Organization:
State Univ. of New York, Buffalo, NY (USA)
OSTI ID:
7061604
Resource Relation:
Other Information: Thesis (Ph. D.)
Country of Publication:
United States
Language:
English

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